US5438066A - Oxa- and thiadiazole derivatives - Google Patents

Oxa- and thiadiazole derivatives Download PDF

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US5438066A
US5438066A US08/144,179 US14417993A US5438066A US 5438066 A US5438066 A US 5438066A US 14417993 A US14417993 A US 14417993A US 5438066 A US5438066 A US 5438066A
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alkyl
alkoxy
halo
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Ian R. Matthews
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Syngenta Ltd
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Zeneca Ltd
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Priority claimed from GB939309964A external-priority patent/GB9309964D0/en
Priority claimed from GB939309965A external-priority patent/GB9309965D0/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/13—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to novel thiadiazole and oxadiazole derivatives, to processes for preparing them, to fungicidal and insecticidal compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants, and insect pests.
  • a compound having the general formula (I), or a stereoisomer thereof wherein A is CH or N; B is OCH 3 or NHCH 3 ; one of L and M is N and the other is S or O, X is an optionally substituted carbocyclic or heterocyclic group; and n is 0 or 1.
  • the compounds of the invention may be obtained in the form of mixtures of (E)- and (Z)-geometric isomers. However, these mixtures can be separated into individual isomers, and this invention embraces such isomers and mixtures thereof in all proportions including those which consist substantially of the (Z)-isomer and those which consist substantially of the (E)-isomer.
  • the (E)-isomer, in which the groups --COB and --OCH 3 are on opposite sides of the olefinic bond, is generally the more fungicidally active and forms a preferred embodiment of the invention. Of particular interest is the group, CH 3 O 2 C.C ⁇ CH.OCH 3 , and especially its (E)-isomer.
  • the 5-membered ring in which one of L and M is N and the other is S or O, is a 1,2,4-thiadiazole or, preferably, a 1,2,4-thiadiazole ring, or a 1,2,4-oxadiazole or, preferably, a 1,3,4-oxadiazole ring.
  • X is an optionally substituted carbocyclic or heterocyclic group, which may be an optionally substituted aryl or optionally substituted heteroaryl group or an optionally substituted alicyclic or an optionally substituted non-aromatic heterocyclic group.
  • Aryl includes phenyl and naphthyl.
  • Heteroaryl includes 5- and 6-membered aromatic rings containing one or more oxygen, sulphur or nitrogen atoms and such rings fused to a benzene ring. Examples of heteroaryl are pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, indolinyl, isoindolinyl, benzofuranyl, benzothiophenyl, benzimidazolinyl, benzoxazolyl and benzthiazolyl.
  • 6-membered heteroaromatic rings containing one, two or three nitrogen atoms ie pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl rings.
  • Alicyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornanyl, adamantyl, cyclopentenyl, cycloheptenyl, cyclooctenyl, cyclohexenyl and norbornenyl groups.
  • Non-aromatic heterocyclic groups include oxiranyl, aziridinyl, azetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl and morpholino groups.
  • Substituents which may be present in the optionally substituted carbocyclic or heterocyclic group include one or more of the following: halo, hydroxy, mercapto, C 1-4 alkyl (especially methyl and ethyl), C 2-4 alkenyl (especially allyl), C 2-4 alkynyl (especially propargyl), C 1-4 alkoxy (especially methoxy), C 2-4 alkenyloxy (especially allyloxy), C 2-4 alkynyloxy (especially propargyloxy), halo(C 1-4 )alkyl (especially trifluoromethyl), halo(C 1-4 )alkoxy (especially trifluoromethoxy), C 1-4 alylthio (especially methylthio), hydroxy(C 1-4 )alkyl, C 1-4 alkoxy(C 1-4 )alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl(C 1-4 )alkyl, optionally substituted methyl
  • Substituents which may be present in the aryl or heteroaryl rings of any of the foregoing substituents include one or more of the following: halo, hydroxy, mercapto, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 2-4 alkenyloxy, C 2-4 alkynyloxy, halo(C 1-4 )alkyl, halo(C 1-4 )-alkoxy, C 1-4 alkylthio, hydroxy(C 1-4 )alkyl, C 1-4 alkoxy(C 1-4 )alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl(C 1-4 )alkyl, alkanoyloxy, benzoyloxy, cyano, thiocyanato, nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --SO 2 R'
  • Substituted alicyclic and non-aromatic heterocyclic groups include, in particular, those groups substituted by alkyl, haloalkyl, cycloalkylalkyl, alkenyl and haloalkenyl. Alicyclic groups are typically substituted by methyl.
  • alkyl moieties and the alkyl moiety of alkoxy suitably contain from 1 to 6, for example from 1 to 4, carbon atoms in the form of straight or branched chains. Examples are methyl, ethyl, n- and iso- propyl, and n-, sec-, iso- and tert- butyl.
  • Alkenyl and alkynyl moieties suitably contain from 2 to 6, for example from 2 to 4, carbon atoms in the form of straight or branched chains.
  • the alkenyl moieties may have either the (E)- or (z)-configuration. Examples are vinyl, allyl and propargyl.
  • Halogen is typically fluorine, chlorine or bromine.
  • the invention provides a compound of the general formula (I) wherein A is CH or N; B is OCH 3 ; one of L and M is N and the other is S or O; X is phenyl optionally substituted with halo (especially fluoro, chloro or bromo), C 1-4 alkyl (especially methyl or ethyl), halo(C 1-4 )alkyl (especially trifluoromethyl), C 1-4 alkoxy (especially methoxy or ethoxy), halo(C 1-4 )alkoxy (especially trifluoromethoxy), C 1-4 alkoxy(C 1-4 )alkyl (especially methoxymethyl), methylenedioxy, ethylenedioxy, cyano, nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --COR', --SO 2 R' or --OSO 2 R' in which R' and R" are independently hydrogen or C 1-4 alkyl;
  • the invention provides a compound of the general formula (I) wherein A is CH or N; B is OCH 3 ; one of L and M is N and the other is S or O; X is 2-, 3- or 4-pyridinyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 3- or 4-pyridazinyl or 2-1,3,5-triazinyl, any one of which is optionally substituted with halo (especially fluoro or chloro), C 1-4 alkyl (especially methyl), halo(C 1-4 )alkyl (especially trifluoromethyl), C 1-4 alkoxy (especially methoxy or ethoxy) or halo(C 1-4 )alkoxy (especially trifluoromethoxy or trifluoroethoxy); and n is 0 or 1.
  • Particular compounds of this type include those where A is CH; L is S; M is N; and n is 0, and where A is CH; L is N; M is 0; and n is 0.
  • the invention provides a compound of the general formula (I) wherein A is CH or N; B is OCH 3 ; one of L and M is N and the other is S or O; X is C 3-6 cycloalkyl optionally substituted with C 1-6 alkyl, halo(C 1-4 )alkyl, C 3-6 cycloalkyl(C 1-4 ) alkyl, C 2-6 alkenyl or halo(C 2-6 )alkenyl; and n is 0 or 1.
  • Particular compounds of this type include those where A is CH; L is S; M is N; and n is 0, and where A is CH; L is N; M is 0; and n is 0.
  • the present invention is illustrated by compounds of the general formula (I) listed in Tables 1 to 16 and in Tables 1' to 16' which follow. Throughout these Tables the group BOC.C ⁇ A.OCH 3 has the (E)-configuration.
  • Table 2 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH 3 , L is S, M is N, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 3 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH 3 , L is S, M is N, n is 0 and X has the value listed for the correspondingly numbered compound in Table 3.
  • Table 4 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH 3 , L is S, M is N, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 5 comprises 370 compounds of the general formula (I), wherein A is CH, B is OCH 3 , L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 6 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH 3 , L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 7 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH 3 , L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 8 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH 3 , L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 9 comprises 370 compounds of the general formula (I), wherein A is CH, B is OCH 3 , L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 10 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH 3 , L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 11 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH 3 , L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 12 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH 3 , L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 13 comprises 370 compounds of the general formula (I), wherein A is CH, B is OCH 3 , L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 14 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH 3 , L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 15 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH 3 , L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Table 16 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH 3 , L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
  • Tables 1' to 16' correspond to Tables 1 to 16, respectively, except that in Tables 1' to 4' and 9' to 12' L, in the general formula (I), is O instead of S and in Tables 5' to 8' and Tables 13' to 16' M, in the general formula (I), is O instead of S.
  • the 370 compounds in each of Tables 1' to 16' are the same as those in each of the corresponding Tables 1 to 16 except that the compounds in Tables 1' to 16' contain an oxathiazole ring instead of the thiadiazole ring contained by the compounds in Tables 1 to 16.
  • Table 17 shows melting point or selected proton NMR data obtained at 270 MHz for certain compounds described in Tables 1 to 16. Chemical shifts are measured at 20° C. unless otherwise stated and in ppm from tetramethyl silane. Deuterochloroform was used as solvent unless otherwise stated. The following abbreviations are used:
  • Compounds of the present invention can be prepared by reacting together a phenol of the general formula (II), wherein A and B have the meanings given before, with a thiadiazole or oxadiazole derivative of the general formula (III), wherein L, M, X and n have the meanings given before and Y is a suitable leaving group such as methylsulphonyl, tosyl or halo, for example chloro, in a suitable solvent, such as N,N-dimethylformamide, and in the presence of a suitable base, such as potassium carbonate or sodium hydride.
  • a suitable solvent such as N,N-dimethylformamide
  • a suitable base such as potassium carbonate or sodium hydride.
  • the phenol and thiadiazole or oxadiazole derivative are dissolved in the solvent at a temperature of about 5° C.
  • the base is stirred in a solution of the phenol in part of the solvent at a temperature of about 5° C. and the thiadiazole or oxadiazole added in the remaining solvent.
  • the reaction mixture is then stirred at room temperature for several hours, before extraction of the desired product.
  • Phenols of the formula (II) can be prepared by methods described in, for example, EP-A-0242081, EP-A-0398692 and GB-A-2249092.
  • Thiadiazole and oxadiazole derivatives of the formula (III) can be prepared by adapting standard literature methods (see, for example, J. Goerdeler, H. Grochopp and U. Sommerlad, Chem. Ber., 1957, 90, 182 for 1,2,4-thiadiazoles, S. Kubota, K. Toyooka, J. Ikeda, N. Yamamoto and M Shibuya, J. Chem. Soc. Perkin Trans. 1, 1983, 967 or EP-A-0486798 for 1,3,4-thiadiazoles, C. Moussebois and F. Eloy, Helv. Chim. Acta, 47, 838 (1964), P. C. Unangst, G. P. Shrum, D.
  • 1,2,4-Thiadiazoles of the formula (III), where L is tosyl (p-tolylsulphonyl) may be obtained by the thermolysis of 5-substituted 1,3,4-oxathiazole-2-ones in excess p-tolylsulphonylnitrile conveniently in a hydrocarbon solvent, such as dodecane (see R. K. Howe and J. E. Franz, J. Org. Chem., 39, 962 (1974)).
  • the 1,3,4-oxathiazolones can be prepared by reaction of acid amides with chlorocarbonylsulphenyl chloride by known procedures (see, for example, GB-A-1079348).
  • 1,2,4-Thiadiazoles of the formula (III), where L is methylsulphonyl may be prepared by the reaction of methyl iodide followed by 3-chloroperoxybenzoic acid with 3-substituted-5-mercapto-1,2,4-thiazoles.
  • the 5-mercapto-1,2,4-thiazoles can be prepared by the reaction of amidines with carbon disulphide and sulphur in the presence of sodium methoxide in methanol (see GB-A-1116198).
  • 1,2,4-Oxadiazoles of the formula (III), where L is chloro may be obtained by reacting 3-substituted 1,2,4-oxadiazol-5-ones with phosphoryl chloride.
  • the 1,2,4-oxadiazolones can be prepared by acylation of amidoximes and cyclization of the resulting intermediate (see EP-A-0446010 or P. C. Unangst, G. P. Shrum, D. T. Connor, R. D. Dyer and D. J. Schrier, J. Med. Chem., 35, 3691 (1992)).
  • Amidoximes are obtained by known methods, for example by the action of hydroxylamine on the appropriate nitriles.
  • the invention compounds of formula (I) may be prepared from a compound of the formula (IV), wherein L, M, X and n have the meanings given before and W is a group which can be converted by standard procedures described in the literature into the group BOC.C ⁇ A.OCH 3 .
  • W is the group CH 3 CO 2 C.C ⁇ CH.OH, CH 3 CO 2 C.C ⁇ N.OH or CH 3 NHOC.C ⁇ N.OH it may be converted to the appropriate group BOC.C ⁇ A.OCH 3 by methylation with a compound CH 3 L, wherein L is a leaving group such as halo or CH 3 SO 2 .O, in the presence of a convenient base (such as sodium hydride or potassium carbonate).
  • W is the phenylglyoxylic acid derivative, CO.CO 2 CH 3 or CO.CONHCH 3 , it may be converted to the appropriate group BOC.C ⁇ A.OCH 3 by treatment with the Wittig reagent Ph 3 P ⁇ CH.OCH 3 , wherein Ph is phenyl, or with methylhydroxylamine.
  • the compounds (IV) can be prepared by reacting a phenol of the general formula (IIa) with a thiadiazole or oxadiazole derivative of the general formula (III), as described above for the phenol (II).
  • the phenol (IIa) can conveniently be prepared from appropriately substituted phenylacetic acid derivatives by methods known in the literature (see, for example, EP-A-0178826, EP-A-0254426, EP-A-0278595, EP-A-0299694 and EP-A-0398692).
  • the compounds of formula (I), wherein A is CH or N and B is NHCH 3 can also be prepared from the corresponding compounds wherein A is CH or N and B is OH, by methods set out in the literature and in other ways described in EP-A-0398692.
  • the invention provides processes for preparing compounds of formula (I).
  • the compounds of formula (I) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae on rice and wheat and other Pyricularia spp. on other hosts; Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g.
  • compositions show a broad range of activities against fungi in vitro.
  • the compounds may move acropetally/locally in plant tissue. Moreover, the compounds may be volatile enough to be active in the vapour phase against fungi on the plant.
  • the invention therefore provides a method of combating fungi which comprises applying to a plant, to a seed of a plant or to the locus of the plant or seed a fungicidally effective amount of a compound as hereinbefore defined, or a composition containing the same.
  • the compounds may be used directly for agricultural purposes but are more conveniently formulated into compositions using a carrier or diluent.
  • the invention thus provides fungicidal compositions comprising a compound as hereinbefore defined and an acceptable carrier or diluent therefor. It is preferred that all compositions, both solid and liquid formulations, comprise 0.0001 to 95%, more preferably 1 to 85%, for example 1 to 25% or 25 to 60%, of a compound as hereinbefore defined.
  • the compounds of the invention When applied the foliage of plants, the compounds of the invention are applied at rates of 0.1 g to 10 kg, preferably 1 g to 8 kg, more preferably 10 g to 4 kg, of active ingredient (invention compound) per hectare.
  • the compounds of the invention are used at rates of 0.0001 g (for example 0.0001 g or 0.05 g) to 10 g, preferably 0.005 g to 8 g, more preferably 0.005 g to 4 g, of active ingredient (invention compound) per kilogram of seed.
  • the compounds can be applied in a number of ways. For example, they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules.
  • Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted, or to the soil generally, to paddy water or to hydroponic culture systems.
  • the invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods or applied by land or aerial irrigation systems.
  • plant as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments.
  • the compounds are preferably used for agricultural and horticultural purposes in the form of a composition.
  • the type of composition used in any instance will depend upon the particular purpose envisaged.
  • the fungicidal compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay.
  • a solid diluent or carrier for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay.
  • Such granules can be preformed granules suitable for application to the soil without further treatment.
  • These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered
  • compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrol-idone, propylene glycol or N,N-dimethylformamide).
  • the compositions may also be in the form of water dispersible powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids.
  • the powders and granules may also contain fillers and suspending agents.
  • the fungicidal compositions may also be in the form of soluble powders or granules, or in the form of solutions in polar solvents.
  • Soluble powders may be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank.
  • polar solvents such as ketones, alcohols and glycol ethers.
  • Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent.
  • organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.
  • Aqueous suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included to stop the solid settling.
  • Fungicidal compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure of a propellant, e.g. fluorotrichloromethane or dichlorodifluoromethane.
  • a propellant e.g. fluorotrichloromethane or dichlorodifluoromethane.
  • the invention compounds can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.
  • the compounds may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
  • additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surface the different compositions can be better adapted for various utilities.
  • Other additives may be included to improve the biological efficacy of the various formulations.
  • Such additives can be surface active materials to improve the setting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives, for example, certain mineral oil and natural plat oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.
  • the invention compounds can be used as mixtures with fertilisers (e.g. nitrogen-, potassium- or phosphorous-containing fertilisers).
  • Compositions comprising only granules of fertiliser incorporating, for example coated with, a compound of formula (I) are preferred. Such granules suitably contain up to 25% by weight of the compound.
  • the invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or metal complex thereof.
  • Water dispersible powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants, e.g. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.
  • Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethylammonium bromide.
  • Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates).
  • Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol.
  • Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, alkyl glucosides, polysaccharides and the lecithins and the condensation products of the said partial esters with ethylene oxide.
  • Suitable suspending agents are hydrophilic colloids (for example, polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite.
  • Fungicidal compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use.
  • Theses concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment.
  • the concentrates may conveniently contain up to 95%, suitably 1-85%, for example 1-25% or 25-60%, by weight of the active ingredient.
  • aqueous preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0001 to 10%, for example 0.005 to 10%, by weight of active ingredient may be used.
  • the fungicidal compositions of this invention may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.
  • the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of general formula (I) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I).
  • fungicidal compounds which may be included in the composition of the invention are (RS)-1-aminopropylphosphonic acid, (RS)-4-(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-yl-methyl)butyronitrile, (Z)-N-but-2-enyloxmethyl-2-chloro-2',6'-diethylacetanilide, 1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 4-(2,2-difluoro-1,3-benzodioxol-4-yl)pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylobenzimidazole-1-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxol-(4,5-g)quinoline-7-carboxylic acid
  • the compounds of formula (I) may also be used to combat and control infestations of insect pests and also other invertebrate pests, for example, acarine pests.
  • insect and acarine pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, forestry, the storage or products of vegetable origin, such as fruit, grain and timber, and also those pests associated with the transmission of diseases of man and animals.
  • compositions which include in addition to the insecticidally active ingredient or ingredients of formula I suitable inert diluent or carrier materials, and/or surface active agents.
  • suitable inert diluent or carrier materials and/or surface active agents.
  • the insecticidal compositions may also comprise another pesticidal material, for example another insecticide or acaricide, or a fungicide, or may also comprise an insecticide synergist, such as for example didecyl imidazole, safroxan, or piperonyl butoxide.
  • the insecticidal compositions may be in the form of dusting powders wherein the active ingredient is mixed with a solid diluent or carrier, for example kaolin, bentonite, kieselguhr, or talc, or they may be in the form of granules, wherein the active ingredient is absorbed in a porous granular material for example pumice.
  • a solid diluent or carrier for example kaolin, bentonite, kieselguhr, or talc
  • granules wherein the active ingredient is absorbed in a porous granular material for example pumice.
  • insecticidal composition may be in the form of baits wherein the active ingredient is mixed with a nutrient carrier for example sucrose, yeast, malt extract, cereal or cereal products and optionally an attractant such as a pheromone or pheromone analogue.
  • a nutrient carrier for example sucrose, yeast, malt extract, cereal or cereal products
  • an attractant such as a pheromone or pheromone analogue.
  • insecticidal compositions may be in the form of liquid preparations to be used as dips or sprays, which are generally aqueous dispersions or emulsions of the active ingredient in the presence of one or more known wetting agents, dispersing agents or emulsifying agents (surface active agents) of the type described above of for the fungicidal compositions.
  • the insecticidal compositions may be prepared by dissolving the active ingredient in a suitable solvent, for example, a ketonic solvent such as diacetone alcohol, or a aromatic solvent such as trimethylbenzene and adding the mixture so obtained to water which may contain one or more known wetting, dispersing or emulsifying agents.
  • a suitable solvent for example, a ketonic solvent such as diacetone alcohol, or a aromatic solvent such as trimethylbenzene and adding the mixture so obtained to water which may contain one or more known wetting, dispersing or emulsifying agents.
  • Suitable organic solvents are dimethyl formamide, ethylene dichloride, isopropyl alcohol, propylene glycol and other glycols, diacetone alcohol, toluene, kerosene, white oil, methylnaphthalene, xylenes and trichloroethylene, N-methyl-2-pyrrolidone and tetrahydrofurfuryl alcohol (THFA).
  • the insecticidal compositions which are to be used in the form of aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient or ingredients, the said concentrate to be diluted with water before use. These concentrates are often required to withstand storage for prolonged periods and after such storage, to be capable of dilution with water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment.
  • the concentrates may contain 10-85% by weight of the active ingredient or ingredients. When diluted to form aqueous preparations such preparations may contain varying amounts of the active ingredients depending upon the purpose for which they are to be used. For agricultural or horticultural purposes, an aqueous preparation containing between 0.0001% and 0.1% by weight of the active ingredient (approximately equivalent to from 5-2000 g/ha) is particularly useful.
  • insecticidal compositions are applied to the pests, to the locus of the pests, to the habitat of the pests, to growing plants liable to infestation by the pests, or, where there is systemic uptake by plants, to the soil surrounding plants liable to infestation, by any of the known means of applying pesticidal compositions, for example, by dusting or spraying.
  • the compounds of the invention may be the sole active ingredient of the insecticidal composition or they may be admixed with one or more additional active ingredients such as insecticides, insecticide synergists, herbicides, fungicides or plant growth regulators where appropriate.
  • additional active ingredients for inclusion in admixture with the compounds of the invention may be compounds which will broaden the spectrum of activity of the compounds of the invention or increase their persistence in the location of the pest. They may synergise the activity of the compound of the invention of complement the activity for example by increasing the speed of effect, improving knockdown or overcoming repellency. Additionally multi-component mixtures of this type may help to overcome or prevent the development of resistance to individual components.
  • insecticide insecticide, herbicide or fungicide included in the mixture will depend upon its intended utility and the type of complementary action required.
  • suitable insecticides include the following:
  • a) Pyrethroids such as permethrin, esfenvalerate, deltamethrin, cyhalothrin in particular lambda-cyhalothrin, cypermethrin, alpha cypermethrin, bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids for example ethofenprox, natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin, or 5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl) cyclopropane carboxylate;
  • Organophosphates such as profenofos, sulprofos, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chloropyrifos, phosalone, fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl, fenitrothion or diazinon;
  • Carbamates including aryl carbamates
  • pirimicarb cloethocarb, carbofuran, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur or oxamyl
  • cloethocarb carbofuran
  • ethiofencarb aldicarb
  • thiofurox carbosulfan
  • bendiocarb bendiocarb
  • fenobucarb propoxur or oxamyl
  • Organic tin compounds such as cyhexatin, fenbutatin oxide, or azocyclotin;
  • Macrolides such as avermectins or milbemycins, for example such as abamectin, ivermectin, and milbemycin;
  • Hormones such as pheromones
  • Organochlorine compounds such as benzene hexachloride, DDT, chlordane or dieldrin.
  • Amidines such as chlordimeform or amitraz.
  • insecticides having particular targets may be employed in the mixture if appropriate for the intended utility of the mixture.
  • selective insecticides for particular crops for example stemborer specific insecticides for use in rice such as cartap or buprofezin can be employed.
  • insecticides specific for particular insect species/stages for example ovo-larvicides such as clofentezine, flubenzimine, hexythiazox and tetradifon, acaricides such as dicofol, propargite, bromopropylate, chlorobenzilate, or growth regulators such as hydramethylnon, cyromazine, methoprene, hydroprene, chlorfluazuron and diflubenzuron may also be included in the compositions.
  • ovo-larvicides such as clofentezine, flubenzimine, hexythiazox and tetradifon
  • acaricides such as dicofol, propargite, bromopropylate, chlorobenzilate
  • growth regulators such as hydramethylnon, cyromazine, methoprene, hydroprene, chlorfluazuron and diflubenzuron
  • suitable insecticide synergists for use in the compositions include piperonyl butoxide, sesamex, and dodecyl imidazole.
  • Suitable herbicides, fungicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
  • An example of a rice selective herbicide which can be included is propanil, an example of a plant growth regulator for use in cotton is "Pix", and examples of fungicides for use in rice include blasticides such as blasticidin-S.
  • the ratio of the compound of the invention to the other active ingredient in the composition will depend upon a number of factors including type of target, effect required from the mixture etc.
  • the additional active ingredient of the composition will be applied at about the rate as it is usually employed, or at a slightly lower rate if synergism occurs.
  • the compounds of formula I and insecticidal compositions comprising them have shown themselves active against a variety of insect and other invertebrate pests. They are particularly useful in controlling sucking pests such as aphids and mites.
  • Compounds of the present invention are also generally characterised by a relatively broad spectrum of activity which may include Lepidoptera and Coleoptera in addition to public health pests such as flies and cockroaches.
  • organophosphate, pyrethroid or cyclodiene (for example lindane or dieldrin) resistant strains of public and animal health pests They may also be active against organophosphate, pyrethroid or cyclodiene (for example lindane or dieldrin) resistant strains of public and animal health pests. They may be effective in combating both susceptible and resistant strains of the pests in their adult and immature stages of growth, and may be applied to the infested host animal by topical, oral or parenteral administration.
  • the solution was poured into water and the organic material extracted with ether three times.
  • the compounds were tested against a variety of foliar fungal diseases of plants.
  • the technique employed was as follows.
  • the plants were grown in John Innes Potting Compost (No 1 or 2) in 4 cm diameter minipots.
  • the test compounds were formulated either by bead milling with aqueous Dispersol T or as a solution in acetone or acetone/ethanol which was diluted to the required concentration immediately before use.
  • the formulations (100 ppm active ingredient) were sprayed on to the foliage or applied to the roots of the plants in the soil.
  • the sprays were applied to maximum retention and the root drenches to a final concentration equivalent to approximately 40 ppm a.i. in dry soil. Tween 20 was added to give a final concentration of 0.05% when the sprays were applied to cereals.
  • the compounds were applied to the soil (roots) or to the foliage (by spraying) one or two days before the plant was inoculated with the disease.
  • An exception was the test on Erysiphe graminis in which the plants were inoculated 24 hours before treatment.
  • Foliar pathogens were applied by spray as zoosporangial suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to fourteen days according to the disease and environment.
  • the disease level present (i.e. leaf area covered by actively sporulating disease) on each of the treated plants was recorded using the following assessment scale:
  • This calculated POCO value is then rounded to the nearest of the values in the 9-point assessment scale shown above. In this particular example, the POCO value would be rounded to 30. If the calculated POCO falls exactly mid-way between two of the points, it is rounded to the lower of the two values.
  • the activity of the compounds of formula (I) was determined using a variety of pests.
  • the pests were treated with a liquid composition containing 250 parts per million (ppm) by weight of the compound except in the case of Meloidogyne incognita, which was treated with a liquid composition containing 6.25 ppm by weight of the compound in an in vitro test.
  • the compositions were made by dissolving the compound in acetone and ethanol (50:50) mixture and diluting the solutions with water containing 0.1% by weight of a wetting agent sold under the trade name "SYNPERONIC” NP8 (further diluting to 6.25 ppm in the case of Meloidogyne incognita) until the liquid composition contained the required concentration of the compound.
  • SYNPERONIC is a Registered Trade Mark.
  • the test procedure adopted with regard to each pest was basically the same and comprised supporting a number of the pests on a medium which was usually a substrate, a host plant or a foodstuff on which the pests feed, and treating either or both the medium and the pests with the compositions.
  • the mortality of the pests was then assessed at periods usually varying from two to five days after the treatment with the exception of Musca domestica, for which an additional initial knockdown assessment was made.
  • the results of the tests are presented in Table 19 for each of the compounds.
  • the results indicate a grading of mortality (or knockdown in the case of Musca domestica), designated as A, B or C wherein A indicates 80-100% mortality, B indicates 40-79% mortality and C indicates 0-39% mortality.
  • the pest species is designated by a letter code.

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Abstract

Fungicidal and insecticidal compounds having the general formula (I): ##STR1## or a stereoisomer thereof, wherein A is CH or N; B is OCH3 or NHCH3 ; one of L and M is N and the other is S or O; X is an optionally substituted carbocyclic or heterocyclic group; and n is 0 or 1.

Description

The present invention relates to novel thiadiazole and oxadiazole derivatives, to processes for preparing them, to fungicidal and insecticidal compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants, and insect pests.
Certain derivatives of 5-membered heterocycles, including 1,3,4-thiadiazole, are described in EP-A-0256667 together with their use as fungicides and insecticides. In these derivatives, the heterocycle is linked to a methyl 2-phenyl-3-methoxyacrylate group.
According to the present invention there is provided a compound having the general formula (I), or a stereoisomer thereof, wherein A is CH or N; B is OCH3 or NHCH3 ; one of L and M is N and the other is S or O, X is an optionally substituted carbocyclic or heterocyclic group; and n is 0 or 1.
Because the double bond of the group, BOC.C═A.OCH3, is unsymmetrically substituted, the compounds of the invention may be obtained in the form of mixtures of (E)- and (Z)-geometric isomers. However, these mixtures can be separated into individual isomers, and this invention embraces such isomers and mixtures thereof in all proportions including those which consist substantially of the (Z)-isomer and those which consist substantially of the (E)-isomer. The (E)-isomer, in which the groups --COB and --OCH3 are on opposite sides of the olefinic bond, is generally the more fungicidally active and forms a preferred embodiment of the invention. Of particular interest is the group, CH3 O2 C.C═CH.OCH3, and especially its (E)-isomer.
The 5-membered ring in which one of L and M is N and the other is S or O, is a 1,2,4-thiadiazole or, preferably, a 1,2,4-thiadiazole ring, or a 1,2,4-oxadiazole or, preferably, a 1,3,4-oxadiazole ring.
X is an optionally substituted carbocyclic or heterocyclic group, which may be an optionally substituted aryl or optionally substituted heteroaryl group or an optionally substituted alicyclic or an optionally substituted non-aromatic heterocyclic group.
Aryl includes phenyl and naphthyl. Heteroaryl includes 5- and 6-membered aromatic rings containing one or more oxygen, sulphur or nitrogen atoms and such rings fused to a benzene ring. Examples of heteroaryl are pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, indolinyl, isoindolinyl, benzofuranyl, benzothiophenyl, benzimidazolinyl, benzoxazolyl and benzthiazolyl. Of particular interest are 6-membered heteroaromatic rings containing one, two or three nitrogen atoms, ie pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl rings.
Alicyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornanyl, adamantyl, cyclopentenyl, cycloheptenyl, cyclooctenyl, cyclohexenyl and norbornenyl groups. Non-aromatic heterocyclic groups include oxiranyl, aziridinyl, azetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl and morpholino groups.
Substituents which may be present in the optionally substituted carbocyclic or heterocyclic group include one or more of the following: halo, hydroxy, mercapto, C1-4 alkyl (especially methyl and ethyl), C2-4 alkenyl (especially allyl), C2-4 alkynyl (especially propargyl), C1-4 alkoxy (especially methoxy), C2-4 alkenyloxy (especially allyloxy), C2-4 alkynyloxy (especially propargyloxy), halo(C1-4)alkyl (especially trifluoromethyl), halo(C1-4)alkoxy (especially trifluoromethoxy), C1-4 alylthio (especially methylthio), hydroxy(C1-4)alkyl, C1-4 alkoxy(C1-4)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, optionally substituted methylenedioxy or ethylenedioxy (especially optionally substituted with fluorine or C1-4 alkyl), optionally substituted aryl (especially optionally substituted phenyl), optionally substituted heteroaryl (especially optionally substituted pyridyl or pyrimidinyl), optionally substituted aryloxy (especially optionally substituted phenoxy), optionally substituted heteroaryloxy (especially optionally substituted pyridyloxy or pyrimidinyloxy), optionally substituted aryl(C1-4)alkyl (especially optionally substituted benxyl, optionally substituted phenethyl and optionally substituted phenyl n-propyl) in which the alkyl moiety is optionally substituted with hydroxy, optionally substituted heteroaryl(C1-4)alkyl (especially optionally substituted pyridyl- or pyrimidinyl(C1-4)alkyl), optionally substituted aryl(C2-4)alkenyl (especially optionally substituted phenylethenyl), optionally substituted heteroaryl(C2-4)alkenyl (especially optionally substituted pyridylethenyl or pyrimidinylethenyl), optionally substituted aryl(C1-4)alkoxy (especially optionally substituted benzyloxy), optionally substituted heteroaryl(C1-4)-alkoxy (especially optionally substituted pyridyl-, or pyrimidinyl(C1-4)-alkoxy), optionally substituted aryloxy(C1-4)alkyl (especially phenoxymethyl), optionally substituted heteroaryloxy(C1-4)alkyl (especially optionally substituted pyridyloxy- or pyrimidinyloxy(C1-4)alkyl), acyloxy (including C1-4 alkanoyloxy (especially acetyloxy) and benzoyloxy), cyano, thiocyanato, nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --OSO2 R', --SO2 R', --COR', --CR'═CR" or --N═CR'R" in which R' and R" are independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C3-6 cycloalkyl(C1-4)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C1-4 alkyl or C1-4 alkoxy.
Substituents which may be present in the aryl or heteroaryl rings of any of the foregoing substituents include one or more of the following: halo, hydroxy, mercapto, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C2-4 alkenyloxy, C2-4 alkynyloxy, halo(C1-4)alkyl, halo(C1-4)-alkoxy, C1-4 alkylthio, hydroxy(C1-4)alkyl, C1-4 alkoxy(C1-4)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, alkanoyloxy, benzoyloxy, cyano, thiocyanato, nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --SO2 R', --OSO2 R', --COR', --CR'═NR" or N═CR'R" in which R' and R" have the meanings given above.
Substituted alicyclic and non-aromatic heterocyclic groups include, in particular, those groups substituted by alkyl, haloalkyl, cycloalkylalkyl, alkenyl and haloalkenyl. Alicyclic groups are typically substituted by methyl.
All alkyl moieties and the alkyl moiety of alkoxy suitably contain from 1 to 6, for example from 1 to 4, carbon atoms in the form of straight or branched chains. Examples are methyl, ethyl, n- and iso- propyl, and n-, sec-, iso- and tert- butyl.
Alkenyl and alkynyl moieties suitably contain from 2 to 6, for example from 2 to 4, carbon atoms in the form of straight or branched chains. The alkenyl moieties, where appropriate, may have either the (E)- or (z)-configuration. Examples are vinyl, allyl and propargyl.
Halogen is typically fluorine, chlorine or bromine.
In one aspect, the invention provides a compound of the general formula (I) wherein A is CH or N; B is OCH3 ; one of L and M is N and the other is S or O; X is phenyl optionally substituted with halo (especially fluoro, chloro or bromo), C1-4 alkyl (especially methyl or ethyl), halo(C1-4)alkyl (especially trifluoromethyl), C1-4 alkoxy (especially methoxy or ethoxy), halo(C1-4)alkoxy (especially trifluoromethoxy), C1-4 alkoxy(C1-4)alkyl (especially methoxymethyl), methylenedioxy, ethylenedioxy, cyano, nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --COR', --SO2 R' or --OSO2 R' in which R' and R" are independently hydrogen or C1-4 alkyl; and n is 0 or 1. Particular compounds of this type include those where A is CH; L is S; M is N; and n is 0, and where A is CH; L is N; M is 0; and n is 0.
In another aspect, the invention provides a compound of the general formula (I) wherein A is CH or N; B is OCH3 ; one of L and M is N and the other is S or O; X is 2-, 3- or 4-pyridinyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 3- or 4-pyridazinyl or 2-1,3,5-triazinyl, any one of which is optionally substituted with halo (especially fluoro or chloro), C1-4 alkyl (especially methyl), halo(C1-4)alkyl (especially trifluoromethyl), C1-4 alkoxy (especially methoxy or ethoxy) or halo(C1-4)alkoxy (especially trifluoromethoxy or trifluoroethoxy); and n is 0 or 1. Particular compounds of this type include those where A is CH; L is S; M is N; and n is 0, and where A is CH; L is N; M is 0; and n is 0.
In yet another aspect, the invention provides a compound of the general formula (I) wherein A is CH or N; B is OCH3 ; one of L and M is N and the other is S or O; X is C3-6 cycloalkyl optionally substituted with C1-6 alkyl, halo(C1-4)alkyl, C3-6 cycloalkyl(C1-4) alkyl, C2-6 alkenyl or halo(C2-6)alkenyl; and n is 0 or 1. Particular compounds of this type include those where A is CH; L is S; M is N; and n is 0, and where A is CH; L is N; M is 0; and n is 0.
The present invention is illustrated by compounds of the general formula (I) listed in Tables 1 to 16 and in Tables 1' to 16' which follow. Throughout these Tables the group BOC.C═A.OCH3 has the (E)-configuration.
              TABLE 1                                                     
______________________________________                                    
Table 1 comprises 370 compounds of the general formula (I),               
wherein A is CH, B is OCH.sub.3, L is S, M is N, n is O and X             
has the value listed.                                                     
Com-                 Com-                                                 
pound                pound                                                
No    X              No      X                                            
______________________________________                                    
1     C.sub.6 H.sub.5                                                     
                     186     2-pyrimidinyl                                
2     2-F--C.sub.6 H.sub.4                                                
                     187     4-pyrimidinyl                                
3     3-F--C.sub.6 H.sub.4                                                
                     188     5-pyrimidinyl                                
4     4-F--C.sub.6 H.sub.4                                                
                     189     3-pyridazinyl                                
5     2-Cl--C.sub.6 H.sub.4                                               
                     190     4-pyridazinyl                                
6     3-Cl--C.sub.6 H.sub.4                                               
                     191     2-pyrazinyl                                  
7     4-Cl--C.sub.6 H.sub.4                                               
                     192     2-1,3,5-triazinyl                            
8     2-Br--C.sub.6 H.sub.4                                               
                     193     2-benzoxazolyl                               
9     3-Br--C.sub.6 H.sub.4                                               
                     194     2-benzthiazolyl                              
10    4-Br--C.sub.6 H.sub.4                                               
                     195     4-F-2-pyridinyl                              
11    2,3-F.sub.2 --C.sub.6 H.sub.3                                       
                     196     4-Cl-2-pyridinyl                             
12    2,4-F.sub.2 --C.sub.6 H.sub.3                                       
                     197     2-F-4-pyridinyl                              
13    2,5-F.sub.2 --C.sub.6 H.sub.3                                       
                     198     2-Cl-4-pyridinyl                             
14    2,6-F.sub.2 --C.sub.6 H.sub.3                                       
                     199     2-Cl-6-pyridinyl                             
15    3,5-F.sub.2 --C.sub.6 H.sub.3                                       
                     200     2-F-6-pyridinyl                              
16    2,4,6-F.sub.3 --C.sub.6 H.sub.2                                     
                     201     2-CF.sub.3 -6-pyridinyl                      
17    F.sub.5 -C.sub.6                                                    
                     202     4-CF.sub.3 -2-pyridinyl                      
18    2,3-Cl.sub.2 --C.sub.6 H.sub.3                                      
                     203     2-CH.sub.3 O-3-pyridinyl                     
19    2,4-Cl.sub.2 --C.sub.6 H.sub.3                                      
                     204     2-CH.sub.3 O-4-pyridinyl                     
20    2,5-Cl.sub.2 --C.sub.6 H.sub.3                                      
                     205     2-CH.sub.3 O-5-pyridinyl                     
21    2,6-Cl.sub.2 --C.sub.6 H.sub.3                                      
                     206     2-CH.sub.3 O-6-pyridinyl                     
22    3,5-Cl.sub.2 --C.sub.6 H.sub.3                                      
                     207     3-CH.sub.3 O-2-pyridinyl                     
23    2,4,6-Cl.sub.3 --C.sub.6 H.sub.3                                    
                     208     3-CH.sub.3 O-4-pyridinyl                     
24    Cl.sub.5 -C.sub.6                                                   
                     209     3-CH.sub.3 O-5-pyridinyl                     
25    2-CH.sub.3 --C.sub.6 H.sub.4                                        
                     210     3-CH.sub.3 O-6-pyridinyl                     
26    3-CH.sub.3 --C.sub.6 H.sub.4                                        
                     211     4-CH.sub.3 O-2-pyridinyl                     
27    4-CH.sub.3 --C.sub.6 H.sub.4                                        
                     212     4-CH.sub.3 O-3-pyridinyl                     
28    2-C.sub.2 H.sub.5 --C.sub.6 H.sub.4                                 
                     213     2,6-diF-3-pyridinyl                          
29    3-C.sub.2 H.sub.5 --C.sub.6 H.sub.4                                 
                     214     5-Cl-2-pyrimidinyl                           
30    4-C.sub.2 H.sub.5 --C.sub.6 H.sub.4                                 
                     215     5-F-2-pyrimidinyl                            
31    2-CF.sub.3 --C.sub.6 H.sub.4                                        
                     216     5-CH.sub.3 -2-pyrimidinyl                    
32    3-CF.sub.3 --C.sub.6 H.sub.4                                        
                     217     4-CH.sub.3 O-2-pyrimidinyl                   
33    4-CF.sub.3 --C.sub.6 H.sub.4                                        
                     218     2-CH.sub.3 O-4-pyrimidinyl                   
34    2-CH.sub.3 O--C.sub.6 H.sub.4                                       
                     219     2-CH.sub.3 O-5-pyrimidinyl                   
35    3-CH.sub.3 O--C.sub.6 H.sub.4                                       
                     220     4-CH.sub.3 O-6-pyrimidinyl                   
36    4-CH.sub.3 O--C.sub.6 H.sub.4                                       
                     221     5-CH.sub.3 O-4-pyrimidinyl                   
37    2-CF.sub.3 O--C.sub.6 H.sub.4                                       
                     222     6-CH.sub.3 O-5-pyrimidinyl                   
38    3-CF.sub.3 O--C.sub.6 H.sub.4                                       
                     223     4-C.sub.2 H.sub.5 O-2-pyrimidinyl            
39    4-CF.sub.3 O--C.sub.6 H.sub.4                                       
                     224     2-CF.sub.3 -4-pyrimidinyl                    
40    2-CH.sub.3 OCH.sub.2 --C.sub.6 H.sub.4                              
                     225     4-CF.sub.3 -2-pyrimidinyl                    
41    3-CH.sub.3 OCH.sub.2 --C.sub.6 H.sub.4                              
                     226     4-CF.sub.3 --5-pyrimidinyl                   
42    4-CH.sub.3 OCH.sub.2 --C.sub.6 H.sub.4                              
                     227     4-CF.sub.3 --6-pyrimidinyl                   
43    2-CN--C.sub.6 H.sub.4                                               
                     228     5-CF.sub.3 --6-pyrimidinyl                   
44    3-CN--C.sub.6 H.sub.4                                               
                     229     4-CF.sub.3 CH.sub.2 O-2-                     
                             pyrimidinyl                                  
45    4-CN--C.sub. 6 H.sub.4                                              
                     230     6-CH.sub.3 O-2-benzthiazolyl                 
46    2-NO.sub.2 --C.sub.6 H.sub.4                                        
                     231     2-CH.sub.3 S--C.sub.6 H.sub.4                
47    3-NO.sub.2 --C.sub.6 H.sub.4                                        
                     232     3-CH.sub.3 S--C.sub.6 H.sub.4                
48    4-NO.sub.2 --C.sub.6 H.sub.4                                        
                     233     4-CH.sub.3 S--C.sub.6 H.sub.4                
49    2-NH.sub.2 --C.sub.6 H.sub.4                                        
                     234     2-naphthyl                                   
50    3-NH.sub.2 --C.sub.6 H.sub.4                                        
                     235     cyclopropyl                                  
51    4-NH.sub.2 --C.sub.6 H.sub.4                                        
                     236     cyclobutyl                                   
52    2,3-(CH.sub.3).sub.2 --C.sub.6 H.sub.3                              
                     237     cyclopentyl                                  
53    2,4-(CH.sub.3).sub.2 --C.sub.6 H.sub.3                              
                     238     2-cyclopenten-1-yl                           
54    2,5-(CH.sub.3).sub.2 --C.sub.6 H.sub.3                              
                     239     3-cyclopenten-1-yl                           
55    2,6-(CH.sub.3).sub.2 --C.sub.6 H.sub.3                              
                     240     2-cyclohexen-1-yl                            
56    2-CH.sub.3 --3-NO.sub.2 --C.sub.6 H.sub.3                           
                     241     3-cyclohexen-1-yl                            
57    2-CH.sub.3 --4-NO.sub.2 --C.sub.6 H.sub.3                           
                     242     1-cyclopenten-1-yl                           
58    2-CH.sub.3 --5-NO.sub.2 --C.sub.6 H.sub.3                           
                     243     1-cyclohexen-1-yl                            
59    2-CH.sub.3 --6-NO.sub.2 --C.sub.6 H.sub.3                           
                     244     adamantyl                                    
60    3-CH.sub.3 --2-NO.sub.2 --C.sub.6 H.sub.3                           
                     245     norbornen-2-yl                               
61    3-CH.sub.3 --4-NO.sub.2 --C.sub.6 H.sub.3                           
                     246     norbornan-2-yl                               
62    3-CH.sub.3 --5-NO.sub.2 --C.sub.6 H.sub.3                           
                     247     1-CH.sub.3 -cyclopropyl                      
63    3-CH.sub.3 --6-NO.sub.2 --C.sub.6 H.sub.3                           
                     248     2-CH.sub.3 -cyclopropyl                      
64    2-NO.sub.2 --4-CH.sub.3 --C.sub.6 H.sub.3                           
                     249     1-CH.sub.3 -cyclobutyl                       
65    3-NO.sub.2 --4-CH.sub.3 --C.sub.6 H.sub.3                           
                     250     2-CH.sub.3 -cyclobutyl                       
66    2-CH.sub.3 --3-CN--C.sub.6 H.sub.3                                  
                     251     1-CH.sub.3 -cyclopentyl                      
67    2-CH.sub.3 --4-CN--C.sub.6 H.sub.3                                  
                     252     2-CH.sub.3 -cyclopentyl                      
68    2-CH.sub.3 --5-CN--C.sub.6 H.sub.3                                  
                     253     3-CH.sub.3 -cyclopentyl                      
69    2-CH.sub.3 --6-CN--C.sub.6 H.sub.3                                  
                     254     1-CH.sub.3 -cyclohexyl                       
70    3-CH.sub.3 --2-CN--C.sub.6 H.sub.3                                  
                     255     2-CH.sub.3 -cyclohexyl                       
71    3-CH.sub.3 --4-CN--C.sub.6 H.sub.3                                  
                     256     3-CH.sub.3 -cyclohexyl                       
72    3-CH.sub.3 --5-CN--C.sub.6 H.sub.3                                  
                     257     4-CH.sub.3 -cyclohexyl                       
73    3-CH.sub.3 --6-CN--C.sub.6 H.sub.3                                  
                     258     cyclohexyl                                   
74    4-CH.sub.3 --2-CN--C.sub.6 H.sub.3                                  
                     259     cycloheptyl                                  
75    4-CH.sub.3 --3-CN--C.sub.6 H.sub.3                                  
                     260     2,2,3,3-(CH.sub.3).sub.4 -                   
                             cyclopropyl                                  
76    2-F-3-NO.sub.2 --C.sub.6 H.sub.3                                    
                     261     4-cycloocten-1-yl                            
77    2-F-4-NO.sub.2 --C.sub.6 H.sub.3                                    
                     262     4-cyclohepten-1-yl                           
78    2-F-5-NO.sub.2 --C.sub.6 H.sub.3                                    
                     263     2-CH.sub.3 -norbornan-2-yl                   
79    2-F-6-NO.sub.2 --C.sub.6 H.sub.3                                    
                     264     3-CH.sub.3 -1-cyclohexen-4-yl                
80    3-F-2-NO.sub.2 --C.sub.6 H.sub.3                                    
                     265     2-CH.sub.2 ═CH-cyclopropyl               
81    3-F-4-NO.sub.2 --C.sub.6 H.sub.3                                    
                     266     2-CH.sub.3 -5-norbornen-2-yl                 
82    3-F-5-NO.sub.2 --C.sub.6 H.sub.3                                    
                     267     tetrahydropyran-2-yl                         
83    3-F-6-NO.sub.2 --C.sub.6 H.sub.3                                    
                     268     tetrahydropyran-3-yl                         
84    4-F-2-NO.sub.2 --C.sub.6 H.sub.3                                    
                     269     tetrahydropyran-4-yl                         
85    4-F-3-NO.sub.2 --C.sub.6 H.sub.3                                    
                     270     tetrahydrofuran-2-yl                         
86    2-F-3-CF.sub.3 --C.sub.6 H.sub.3                                    
                     271     tetrahydrofuran-3-yl                         
87    2-F-4-CF.sub.3 --C.sub.6 H.sub.3                                    
                     272     tetrahydrothiopyran-2-yl                     
88    2-F-5-CF.sub.3 --C.sub.6 H.sub.3                                    
                     273     tetrahydrothiopyran-3-yl                     
89    2-F-6-CF.sub.3 --C.sub.6 H.sub.3                                    
                     274     tetrahydrothiopyran-4-yl                     
90    3-F-2-CF.sub. 3 --C.sub.6 H.sub.3                                   
                     275     tetrahydrothiophen-2-yl                      
91    3-F-4-CF.sub.3 --C.sub.6 H.sub.3                                    
                     276     tetrahydrothiophen-3-yl                      
92    3-F-5-CF.sub.3 --C.sub.6 H.sub.3                                    
                     277     cyclooctyl                                   
93    3-F-6-CF.sub.3 --C.sub.6 H.sub.3                                    
                     278     3-thienyl                                    
94    4-F-2-CF.sub.3 --C.sub.6 H.sub.3                                    
                     279     3-furyl                                      
95    4-F-3-CF.sub.3 --C.sub.6 H.sub.3                                    
                     280     3-pyrrolyl                                   
96    2-CH.sub.3 O-3-NO.sub.2 --C.sub.6 H.sub.3                           
                     281     2-Cl-3-CH.sub.3 --C.sub.6 H.sub.3            
97    2-CH.sub.3 O-4-NO.sub.2 --C.sub.6 H.sub.3                           
                     282     2-Cl-4-CH.sub.3 --C.sub.6 H.sub.3            
98    2-CH.sub.3 O-5-NO.sub.2 --C.sub.6 H.sub.3                           
                     283     2-Cl-5-CH.sub.3 --C.sub.6 H.sub.3            
99    2-CH.sub.3 O-6-NO.sub.2 --C.sub.6 H.sub.3                           
                     284     2-Cl-6-CH.sub.3 --C.sub.6 H.sub.3            
100   3-CH.sub.3 O-2-NO.sub.2 --C.sub.6 H.sub.3                           
                     285     3-Cl-2-CH.sub.3 --C.sub.6 H.sub.3            
101   3-CH.sub.3 O-4-NO.sub.2 --C.sub.6 H.sub.3                           
                     286     3-Cl-4-CH.sub.3 --C.sub.6 H.sub.3            
102   3-CH.sub.3 O-5-NO.sub.2 --C.sub.6 H.sub.3                           
                     287     3-Cl-5-CH.sub.3 --C.sub.6 H.sub.3            
103   3-CH.sub.3 O-6-NO.sub.2 --C.sub.6 H.sub.3                           
                     288     3-Cl-6-CH.sub.3 --C.sub.6 H.sub.3            
104   4-CH.sub.3 O-2-NO.sub.2 --C.sub.6 H.sub.3                           
                     289     4-Cl-2-CH.sub.3 --C.sub.6 H.sub.3            
105   4-CH.sub.3 O-3-NO.sub.2 --C.sub.6 H.sub.3                           
                     290     4-Cl-3-CH.sub.3 --C.sub.6 H.sub.3            
106   2-CH.sub.3 O-3-CF.sub.3 --C.sub.6 H.sub.3                           
                     291     2-Cl-3-NO.sub.2 --C.sub.6 H.sub.3            
107   2-CH.sub.3 O-4-CF.sub.3 --C.sub.6 H.sub.3                           
                     292     2-Cl-4-NO.sub.2 --C.sub.6 H.sub.3            
108   2-CH.sub.3 O-5-CF.sub.3 --C.sub.6 H.sub.3                           
                     293     2-Cl-5-NO.sub.2 --C.sub.6 H.sub.3            
109   2-CH.sub.3 O-6-CF.sub.3 --C.sub.6 H.sub.3                           
                     294     2-Cl-6-NO.sub.2 --C.sub.6 H.sub.3            
110   3-CH.sub.3 O-2-CF.sub.3 --C.sub.6 H.sub.3                           
                     295     3-Cl-2-NO.sub.2 --C.sub.6 H.sub.3            
111   3-CH.sub.3 O-4-CF.sub.3 --C.sub.6 H.sub.3                           
                     296     3-Cl-4-NO.sub.2 --C.sub.6 H.sub.3            
112   3-CH.sub.3 O-5-CF.sub.3 --C.sub.6 H.sub.3                           
                     297     3-Cl-5-NO.sub.2 --C.sub.6 H.sub.3            
113   3-CH.sub.3 O-6-CF.sub.3 --C.sub.6 H.sub.3                           
                     298     3-Cl-6-NO.sub.2 --C.sub.6 H.sub.3            
114   4-CH.sub.3 O-2-CF.sub.3 --C.sub.6 H.sub.3                           
                     299     4-Cl-2-NO.sub.2 --C.sub.6 H.sub.3            
115   4-CH.sub.3 O-3-CF.sub.3 --C.sub.6 H.sub.3                           
                     300     4-Cl-3-NO.sub.2 --C.sub.6 H.sub.3            
116   2-CH.sub.3 -3-CH.sub.3 O--C.sub.6 H.sub.3                           
                     301     2-Cl-3-CF.sub.3 --C.sub.6 H.sub.3            
117   2-CH.sub.3 -4-CH.sub.3 O--C.sub.6 H.sub.3                           
                     302     2-Cl-4-CF.sub.3 --C.sub.6 H.sub.3            
118   2-CH.sub.3 -5-CH.sub.3 O--C.sub.6 H.sub.3                           
                     303     2-Cl-5-CF.sub.3 --C.sub.6 H.sub.3            
119   2-CH.sub.3 -6-CH.sub.3 O--C.sub.6 H.sub.3                           
                     304     2-Cl-6-CF.sub.3 --C.sub.6 H.sub.3            
120   3-CH.sub.3 -3-CH.sub.3 O--C.sub.6 H.sub.3                           
                     305     3-Cl-2-CF.sub.3 --C.sub.6 H.sub.3            
121   3-CH.sub.3 -4-CH.sub.3 O--C.sub.6 H.sub.3                           
                     306     3-Cl-4-CF.sub.3 --C.sub.6 H.sub.3            
122   3-CH.sub.3 -5-CH.sub.3 O--C.sub.6 H.sub.3                           
                     307     3-Cl-5-CF.sub.3 --C.sub.6 H.sub.3            
123   3-CH.sub.3 -6-CH.sub.3 O--C.sub.6 H.sub.3                           
                     308     3-Cl-6-CF.sub.3 --C.sub.6 H.sub.3            
124   4-CH.sub.3 -2-CH.sub. 3 O--C.sub.6 H.sub.3                          
                     309     4-Cl-2-CF.sub.3 --C.sub.6 H.sub.3            
125   4-CH.sub.3 -3-CH.sub.3 O--C.sub.6 H.sub.3                           
                     310     4-Cl-3-CF.sub.3 --C.sub.6 H.sub.3            
126   2-F-3-CH.sub.3 --C.sub.6 H.sub.3                                    
                     311     2-Cl-3-Br--C.sub.6 H.sub.3                   
127   2-F-4-CH.sub.3 --C.sub.6 H.sub.3                                    
                     312     2-Cl-4-Br--C.sub.6 H.sub.3                   
128   2-F-5-CH.sub.3 --C.sub.6 H.sub.3                                    
                     313     2-Cl-5-Br--C.sub.6 H.sub.3                   
129   2-F-6-CH.sub.3 --C.sub.6 H.sub.3                                    
                     314     2-Cl-6-Br--C.sub.6 H.sub.3                   
130   3-F-2-CH.sub.3 --C.sub.6 H.sub.3                                    
                     315     3-Cl-2-Br--C.sub.6 H.sub.3                   
131   3-F-4-CH.sub.3 --C.sub.6 H.sub.3                                    
                     316     3-Cl-4-Br--C.sub.6 H.sub.3                   
132   3-F-5-CH.sub.3 --C.sub.6 H.sub.3                                    
                     317     3-Cl-5-Br--C.sub.6 H.sub.3                   
133   3-F-6-CH.sub.3 --C.sub.6 H.sub.3                                    
                     318     3-Cl-6-Br--C.sub.6 H.sub.3                   
134   4-F-2-CH.sub.3 --C.sub.6 H.sub.3                                    
                     319     4-Cl-2-Br--C.sub.6 H.sub.3                   
135   4-F-3-CH.sub.3 --C.sub.6 H.sub.3                                    
                     320     4-Cl-3-Br--C.sub.6 H.sub.3                   
136   2-F-3-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     321     2-Cl-3-CN--C.sub.6 H.sub.3                   
137   2-F-4-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     322     2-Cl-4-CN--C.sub.6 H.sub.3                   
138   2-F-5-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     323     2-Cl-5-CN--C.sub.6 H.sub.3                   
139   2-F-6-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     324     2-Cl-6-CN--C.sub.6 H.sub.3                   
140   3-F-2-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     325     3-Cl-2-CN--C.sub.6 H.sub.3                   
141   3-F-4-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     326     3-Cl-4-CN--C.sub.6 H.sub.3                   
142   3-F-5-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     327     3-Cl-5-CN--C.sub.6 H.sub.3                   
143   3-F-6-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     328     3-Cl-6-CN--C.sub.6 H.sub.3                   
144   4-F-2-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     329     4-Cl-2-CN--C.sub.6 H.sub.3                   
145   4-F-3-CH.sub.3 O--C.sub.6 H.sub.3                                   
                     330     4-Cl-3-CN--C.sub.6 H.sub.3                   
146   2-CN-3-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     331     2-Cl-3-F--C.sub.6 H.sub.3                    
147   2-CN-4-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     332     2-Cl-4-F--C.sub.6 H.sub.3                    
148   2-CN-5-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     333     2-Cl-5-F--C.sub.6 H.sub.3                    
149   2-CN-6-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     334     2-Cl-6-F--C.sub.6 H.sub.3                    
150   3-CN-2-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     335     3-Cl-2-F--C.sub.6 H.sub.3                    
151   3-CN-4-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     336     3-Cl-4-F--C.sub.6 H.sub.3                    
152   3-CN-5-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     337     3-Cl-5-F--C.sub.6 H.sub.3                    
153   3-CN-6-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     338     3-Cl-6-F--C.sub.6 H.sub.3                    
154   4-CN-2-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     339     4-Cl-2-F--C.sub.6 H.sub.3                    
155   4-CN-3-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     340     4-Cl-3-F--C.sub.6 H.sub.3                    
156   2-CN-3-F--C.sub.6 H.sub.3                                           
                     341     2,3-(NO.sub.2).sub.2 --C.sub.6 H.sub.3       
157   2-CN-4-F--C.sub.6 H.sub.3                                           
                     342     2,4-(NO.sub.2).sub.2 --C.sub.6 H.sub.3       
158   2-CN-5-F--C.sub.6 H.sub.3                                           
                     343     2,5-(NO.sub.2).sub.2 --C.sub.6 H.sub.3       
159   2-CN-6-F--C.sub.6 H.sub.3                                           
                     344     2,6-(NO.sub.2).sub.2 --C.sub.6 H.sub.3       
160   3-CN-2-F--C.sub.6 H.sub.3                                           
                     345     3,4-(NO.sub.2).sub.2 --C.sub.6 H.sub.3       
161   3-CN-4-F--C.sub.6 H.sub.3                                           
                     346     3,5-(NO.sub.2).sub.2 --C.sub.6 H.sub.3       
162   3-CN-5-F--C.sub.6 H.sub.3                                           
                     347     2,3-(CF.sub.3).sub.2 --C.sub.6 H.sub.3       
163   3-CN-6-F--C.sub.6 H.sub.3                                           
                     348     2,4-(CF.sub.3).sub.2 --C.sub.6 H.sub.3       
164   4-CN-2-F--C.sub.6 H.sub.3                                           
                     349     2,5-(CF.sub.3).sub.2 --C.sub.6 H.sub.3       
165   4-CN-3-F--C.sub.6 H.sub.3                                           
                     350     2,6-(CF.sub.3).sub.2 --C.sub.6 H.sub.3       
166   2-Cl-3-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     351     3,4-(CF.sub.3).sub.2 --C.sub.6 H.sub.3       
167   2-Cl-4-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     352     3,5-(CF.sub.3).sub.2 --C.sub.6 H.sub.3       
168   2-Cl-5-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     353     2,3-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
169   2-Cl-6-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     354     2,4-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
170   3-Cl-2-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     355     2,5-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
171   3-Cl-4-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     356     2,6-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
172   3-Cl-5-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     357     3,4-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
173   3-Cl-6-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     358     3,5-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
174   4-Cl-2-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     359     2,3-(CN).sub.2 --C.sub.6 H.sub.3             
175   4-Cl-3-CH.sub.3 O--C.sub.6 H.sub.3                                  
                     360     2,4-(CN).sub.2 --C.sub.6 H.sub.3             
176   3,4-OCH.sub.2 O--C.sub.6 H.sub.3                                    
                     361     2,5-(CN).sub.2 --C.sub.6 H.sub.3             
177   3,4-OC.sub.2 H.sub.4 O--C.sub.6 H.sub.3                             
                     362     2,6-(CN).sub.2 --C.sub.6 H.sub.3             
178   C.sub.6 H.sub.11                                                    
                     363     3,4-(CN).sub.2 --C.sub.6 H.sub.3             
179   1-naphthyl     364     3,5-(CN).sub.2 --C.sub.6 H.sub.3             
180   2-thienyl      365     2,3-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
181   2-furyl        366     2,4-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
182   2-pyrrolyl     367     2,5-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
183   2-pyridinyl    368     2,6-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
184   3-pyridinyl    369     3,4-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
185   4-pyridinyl    370     3,5-(OCH.sub.3).sub.2 --C.sub.6 H.sub.3      
______________________________________
TABLE 2
Table 2 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH3, L is S, M is N, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 3
Table 3 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH3, L is S, M is N, n is 0 and X has the value listed for the correspondingly numbered compound in Table 3.
TABLE 4
Table 4 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH3, L is S, M is N, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 5
Table 5 comprises 370 compounds of the general formula (I), wherein A is CH, B is OCH3, L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 6
Table 6 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH3, L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 7
Table 7 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH3, L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 8
Table 8 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH3, L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 9
Table 9 comprises 370 compounds of the general formula (I), wherein A is CH, B is OCH3, L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 10
Table 10 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH3, L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 11
Table 11 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH3, L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 12
Table 12 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH3, L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 13
Table 13 comprises 370 compounds of the general formula (I), wherein A is CH, B is OCH3, L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 14
Table 14 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH3, L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 15
Table 15 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH3, L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLE 16
Table 16 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH3, L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.
TABLES 1' TO 16'
Sixteen tables numbered Tables 1' to 16' correspond to Tables 1 to 16, respectively, except that in Tables 1' to 4' and 9' to 12' L, in the general formula (I), is O instead of S and in Tables 5' to 8' and Tables 13' to 16' M, in the general formula (I), is O instead of S. Thus the 370 compounds in each of Tables 1' to 16' are the same as those in each of the corresponding Tables 1 to 16 except that the compounds in Tables 1' to 16' contain an oxathiazole ring instead of the thiadiazole ring contained by the compounds in Tables 1 to 16.
TABLE 17
Table 17 shows melting point or selected proton NMR data obtained at 270 MHz for certain compounds described in Tables 1 to 16. Chemical shifts are measured at 20° C. unless otherwise stated and in ppm from tetramethyl silane. Deuterochloroform was used as solvent unless otherwise stated. The following abbreviations are used:
s=singlet
tt=triple triplet
d=doublet
q=quartet
t=triplet
m=multiplet
__________________________________________________________________________
Compound No                                                               
(Table No)                                                                
         Melting Point (°C.)/NMR (ppm)                             
__________________________________________________________________________
1(1)     8.2(m, 2H); 7.59(s, 1H); 7.2-7.5(m, 7H); 3.75(s, 3H); 3.6(s,     
         3H).                                                             
1(1')    78-80.                                                           
1(5)     7.80-7.86(m, 2H); 7.58(s, 1H); 7.3-7.48(m, 7H); 3.79(s, 3H);     
         3.65(s, 3H).                                                     
1(5')    3.64(s, 3H); 3.80(s, 3H); 7.28-7.38(m, 2H); 7.40-7.54(m, 4H);    
         7.56-7.60(d, 1H); 7.60(s, 1H); 7.94-7.99(m, 2H).                 
1(13')   3.56(s, 3H), 3.65(s, 3H), 4.09(s, 2H), 7.26-7.41(m, 8H),         
         7.48-7.52(m, 2H).                                                
2(1)     3.60(s, 3H); 3.85(s, 3H); 7.1-7.5(m, 7H); 7.55(s, 1H); 8.1(m,    
         1H).                                                             
2(1')    90-92.                                                           
2(5')    90-92.                                                           
3(1)     3.61(s, 3H); 3.75(s, 3H); 7.12(m, 1H); 7.35-7.46(m, 5H);         
         7.55(s, 1H); 7.88(d, 1H); 7.98(d, 1H).                           
3(2)     3.79(s, 3H); 3.95(s, 3H); 7.12(m, 1H); 7.4(m, 3H); 7.55(m, 2H);  
         7.85(d, 1H); 7.96(d, 1H).                                        
3(4)     130-132.                                                         
3(5')    91-94.                                                           
4(1)     3.6(s, 3H); 3.75(s, 3H); 7.1(t, 2H); 7.37-7.46(m, 4H);           
         7.57(s.1H); 8.18(m, 2H).                                         
4(5')    95-97.                                                           
5(1)     127-129.                                                         
5(5')    95-97.                                                           
6(1)     3.62(s, 3H); 3.75(s, 3H); 7.32- 7.47(m, 6H); 7.55(s, 1H);        
         8.05(d, 1H); 8.19(s, 1H).                                        
6(5')    124-126.                                                         
7(1)     8.1(d, 2H); 7.55(s, 1H); 7.4(m, 6H); 3.75(s, 3H); 3.6(s, 3H).    
7(1')    88-90.                                                           
7(2)     84-86.                                                           
7(4)     148-150.                                                         
7(5')    109-111.                                                         
8(1)     3.60(s, 3H); 3.75(s, 3H); 7.2-8.85(m, 8H); 7.55(s, 1H).          
9(1)     3.6(s, 3H); 3.7(s, 3H); 7.2-7.6(m, 6H); 7.57(s, 1H); 8.1(m,      
         1H);                                                             
         8.35(m, 1H).                                                     
9(5')    128-131.                                                         
10(5')   109.                                                             
17(1)    3.62(s, 3H); 3.74(s, 3H); 7.4(m, 4H); 7.58(s, 1H).               
25(1)    109.                                                             
25(5')   89-91.                                                           
26(1)    2.4(s, 3H); 3.6(s, 3H); 3.75(s, 3H); 7.2-7.5(m, 6H); 7.57(s,     
         1H);                                                             
         8.0(m, 2H).                                                      
26(5')   112-115.                                                         
26(9)    2.32(s, 3H); 3.58(s, 3H); 3.65(s, 3H); 4.1(s, 2H); 7.5(s.1H);    
         7.0-7.45(m, 8H).                                                 
27(1)    2.49(s, 3H); 3.60(s, 3H); 3.73(s, 3H); 7.25(d, 2H); 7.4(m, 4H);  
         7.56(s, 1H); 8.1(d, 2H).                                         
27(5')   96-98.                                                           
31(1)    3.61(s, 3H); 3.74(s, 3H); 7.3-7.65(m, 6H); 7.55(s, 1H);          
         7.8(m, 2H).                                                      
32(1)    3.6(s, 3H); 3.85(s, 3H); 7.58(s, 1H); 7.35-7.75(m, 6H);          
         8.35-8.50(m, 2H).                                                
32(1')   3.64(s, 3H); 3.77(s, 3H); 7.34- 7.61(m, 6H); 7.72-7.76(d, 1H);   
         8.16-8.20(d, 1H), 8.24(s, 1H).                                   
32(2)    64-65.                                                           
32(5)    8.0-8.1(m, 2H); 7.69-7.73(m, 1H); 7.58(s, 1H); 7.55-7.61(m,      
         1H);                                                             
         7.3-7.44(m, 4H); 3.81(s, 3H); 3.66(s, 3H).                       
32(5')   120-122.                                                         
33(1)    85-87.                                                           
33(5')   97-99.                                                           
35(1)    3.6(s, 3H); 3.75(s, 3H); 3.9(s, 2H); 7.0(m, 1H); 7.3-7.5(m,      
         5H);                                                             
         7.55(s, 1H); 7.7-7.85(m, 2H).                                    
35(5')   123-126.                                                         
36(1)    104-106.                                                         
36(5')   107-110.                                                         
38(1)    3.61(s, 3H); 3.75(s, 3H); 7.27(m, 1H); 7.37-7.50(m, 5H);         
         7.57(s, 1H); 8.05(s, 1H); 8.13(d, 1H).                           
38(2)    64-66.                                                           
38(4)    122-124.                                                         
41(1)    3.4(s, 3H); 3.6(s, 3H); 3.75(s, 3H); 4.5(s, 2H); 7.3-7.5(m,      
         6H);                                                             
         7.57(s, 1H); 8.1-8.2(m, 2H).                                     
44(1)    3.6(s, 3H); 3.77(s.3H); 7.4-7.75(m, 6H); 7.65(s.1H); 8.4(m,      
         2H).                                                             
44(5')   147-149.                                                         
45(1)    3.60(s, 3H); 3.77(s, 3H); 7.4(m, 4H); 7.56(s, 1H); 7.72(d, 2H);  
         8.3(d, 2H).                                                      
45(5)    7.93-7.97(d, 2H); 7.72-7.76(d, 2H); 7.57(s, 1H);                 
         7.33-7.43(m, 4H); 3.80(s, 3H); 3.65(s, 3H).                      
45(5')   146-148.                                                         
46(5')   3.68(s, 3H); 3.82(s, 3H); 7.28-7.47(m, 3H); 7.53- 7.57(d, 1H);   
         7.62(s, 1H); 7.70-7.81(m, 2H); 7.91-7.95(m, 1H);                 
         8.04-8.08(m, 1H).                                                
47(1)    3.62(s, 3H); 3.76(s, 3H); 7.3-7.5(m, 4H); 7.58(s, 1H);           
         7.62(t, 1H); 8.3(m, 1H); 8.5(m, 1H); 9.05(s, 1H).                
47(5')   149-149.                                                         
48(1)    150.                                                             
48(5')   117-119.                                                         
176(5')  3.64(s, 3H); 3.80(s, 3H); 6.05(s, 2H); 6.87-6.91(d, 1H);         
         7.28-7.60(m, 7H) -including 7.59(s, 1H).                         
178(1)   1.25-2.0(m, 10H); 2.8(m, 1H); 3.6(s, 3H); 3.72(s, 3H);           
         7.30-7.40(m, 4H); 7.55(s, 1H).                                   
180(1)   3.62(s, 3H); 3.77(s, 3H); 7.1(m, 1H); 7.4(m, 5H); 7.57(s, 1H);   
         7.8(m, 1H).                                                      
180(5')  93-95.                                                           
181(1)   3.6(s, 3H); 3.75(s, 3H); 6.5(m, 1H); 7.1(d, 1H); 7.4(m, 4H);     
         7.55(s, 2H).                                                     
181(5')  3.66(s, 3H); 3.80(s, 3H); 6.56-6.60(m, 1H); 7.04-7.08(d, 1H);    
         7.28-7.37(m, 2H); 7.38-7.46(m, 1H); 7.53-7.61(m, 3H).            
183(1)   3.65(s, 3H); 3.77(s, 3H); 7.35-7.50(m, 5H); 7.57(s, 1H);         
         7.84(m, 1H); 8.23(d, 1H); 8.79(d, 1H).                           
184(5)   3.67(s, 3H); 3.81(s, 3H); 7.33-7.44(m, 5H); 7.59(s, 1H);         
         8.18-8.24(m, 1H); 8.68-8.72(m, 1H); 8.98-9.00(m, 1H).            
191(1)   3.65(s, 3H); 3.8(s, 3H); 7.4(m, 4H); 7.57(s, 1H); 8.7(m, 2H);    
         9.45(s, 1H).                                                     
193(5')  3.68(s, 3H); 3.80(s, 3H); 7.33-7.38(m, 2H); 7.42-7.56(m, 3H);    
         7.57-7.62(m, 2H); 7.67-7.71(m, 1H); 7.86-7.91(m, 1H).            
198(1)   3.62(s, 3H); 3.76(s, 3H); 7.39-7.50(m, 4H); 7.56(s, 1H);         
         7.93-7.97(m, 1H); 8.08(s, 1H); 8.47-8.50(d, 1H).                 
213(1)   3.63(s, 3H); 3.77(s.3H); 6.91-6.95(m, 1H); 7.38-7.46(m, 4H);     
         7.56(s, 1H); 8.61-8.71(q, 1H) (94% by glc; 6% Cl, F-pyridine     
         unknown isomers).                                                
214(1)   3.64(s, 3H); 3.75(s, 3H); 7.38-7.50(m, 4H); 7.55(s, 1H);         
         8.89(s, 2H).                                                     
229(1)   3.62(s, 3H); 3.77(s, 3H); 5.0(q, 2H); 6.95(d, 1H); 7.4(m, 4H);   
         7.58(s, 1H); 8.72(d, 1H).                                        
234(5')  125-127.                                                         
235(1)   0.95-1.11(m, 4H); 2.07-2.17(m, 1H); 3.62(s, 3H); 3.75(s, 3H);    
         7.32-7.44(m, 4H); 7.55(s, 1H).                                   
235(5')  1.06-1.11(m, 4H); 1.99-2.10(m, 1H); 3.66(s, 3H); 3.80(s, 3H);    
         7.24-7.34(m, 2H); 7.35-7.42(m, 1H); 7.48-7.52(m, 1H);            
         7.58(s, 1H).                                                     
236(1)   1.90-2.12(m, 2H); 2.28-2.50(m, 4H); 3.60-3.72(m, 1H);            
         3.62(s, 3H); 3.74(s, 3H); 7.33-7.42(m, 4H); 7.56(s, 1H).         
236(5')  1.92-2.18(m, 2H); 2.34-2.50(m, 4H); 3.56-3.69(m, 1H);            
         3.64(s, 3H); 3.80(s, 3H); 7.24-7.43(m, 3H); 7.51-7.54(d, 1H);    
         7.58(s, 1H).                                                     
237(5')  1.66-1.96(m, 6H); 2.00-2.13(m, 2H); 3.14-3.26(m, 1H);            
         3.64(s, 3H); 3.80(s, 3H); 7.24-7.36(m, 2H); 7.36-7.42(m, 1H);    
         7.51-7.54(d, 1H); 7.57(s, 1H).                                   
237(13') 1.19-1.34(m, 2H); 1.52-1.71(m, 4H); 1.78-1.90(m, 2H);            
         2.22-2.34(m, 1H); 2.72-2.76(d, 2H); 3.65(s, 3H); 3.80(s, 3H);    
         7.25-7.43(m, 3H); 7.50-7.54(d, 1H); 7.58(s, 1H).                 
244(5')  1.70-185(m, 6H); 2.00-2.05(m, 6H); 2.05-2.12(m, 3H); 3.64(s,     
         3H);                                                             
         3.80(s, 3H); 7.52-7.56(d, 1H); 7.58(s, 1H).                      
236(13') 1.10-1.40(m, 5H); 1.44-1.57(m, 3H); 1.86-1.96(m, 1H);            
         2.08(s, 1H); 2.24-2.29(m, 1H); 2.50-2.74(m, 2H); 3.65(s, 3H);    
         3.80(s, 3H); 7.51-7.54(d, 1H); 7.58(s, 1H).                      
246(14') 1.10-1.23(m, 4H); 1.32-1.40(m, 1H); 1.48-1.58(m, 3H);            
         1.83-1.98((s, 1H); 2.09(s, 1H); 2.25-2.30(m, 1H);                
         2.52-2.76(m, 2H); 3.86(s, 3H); 4.00(s, 3H); 7.32-7.38(m, 2H);    
         7.48-7.56(m, 1H); 7.66-7.70(d, 1H).                              
246(16') 1.10-1.27(m, 4H); 1.32-1.40(m, 1H); 1.45-1.57(m, 3H);            
         1.87-1.98(m, 1H); 2.06-2.10(m, 1H); 2.24- 2.30(m, 1H);           
         2.51-2.75(m, 2H); 2.92-2.94(d, 3H); 3.88(s, 3H); 6.80(s, 1H);    
         7.30-7.38(m, 2H); 7.46-7.54(m, 1H); 7.62-7.65(d, 1H).            
         95-97.                                                           
247(1)   60-62.                                                           
247(5')  0.86-0.90(m, 2H); 1.19-1.25(m, 2H); 1.50(s, 3H); 3.64(s, 3H);    
         3.80(s, 3H); 7.22-7.42(m, 3H); 7.49-7.52(d, 1H), 7.58(s, 1H).    
258(5')  1.2-2.1(m, 10H); 2.8(tt, 1H); 3.63(s, 3H); 3.8(s, 3H);           
         7.2-7.55(m, 4H); 7.57(s, 1H).                                    
277(1)   145-147.                                                         
270(1)   1.9-2.4(m, 4H); 3.62(s, 3H); 3.75(s, 3H); 3.9-4.0(m, 1H),        
         4.1-4.18(m, 1H); 5.0(m, 1H); 7.32-7.45(m, 4H); 7.57(s, 1H).      
270(5')  1.94-2.21(m, 2H); 2.29-2.37(q, 2H); 3.64(s, 3H); 3.78(s, 3H);    
         5.00-5.05(t, 1H); 7.24-7.43(m, 3H); 7.50-7.54(d, 1H);            
         7.58(s, 1H).                                                     
278(13') 3.59(s, 3H); 3.70(s, 3H); 4.13(s, 2H); 7.04-7.06(d, 1H);         
         7.19-7.21(m, 1H); 7.24-7.42(m, 4H); 7.49-7.53(d, 1H);            
         7.53(s, 1H).                                                     
__________________________________________________________________________
Compounds of the present invention can be prepared by reacting together a phenol of the general formula (II), wherein A and B have the meanings given before, with a thiadiazole or oxadiazole derivative of the general formula (III), wherein L, M, X and n have the meanings given before and Y is a suitable leaving group such as methylsulphonyl, tosyl or halo, for example chloro, in a suitable solvent, such as N,N-dimethylformamide, and in the presence of a suitable base, such as potassium carbonate or sodium hydride. Conveniently, the phenol and thiadiazole or oxadiazole derivative are dissolved in the solvent at a temperature of about 5° C. and the base added. Alternatively, the base is stirred in a solution of the phenol in part of the solvent at a temperature of about 5° C. and the thiadiazole or oxadiazole added in the remaining solvent. The reaction mixture is then stirred at room temperature for several hours, before extraction of the desired product.
Phenols of the formula (II) can be prepared by methods described in, for example, EP-A-0242081, EP-A-0398692 and GB-A-2249092.
Thiadiazole and oxadiazole derivatives of the formula (III) can be prepared by adapting standard literature methods (see, for example, J. Goerdeler, H. Grochopp and U. Sommerlad, Chem. Ber., 1957, 90, 182 for 1,2,4-thiadiazoles, S. Kubota, K. Toyooka, J. Ikeda, N. Yamamoto and M Shibuya, J. Chem. Soc. Perkin Trans. 1, 1983, 967 or EP-A-0486798 for 1,3,4-thiadiazoles, C. Moussebois and F. Eloy, Helv. Chim. Acta, 47, 838 (1964), P. C. Unangst, G. P. Shrum, D. T. Connor, R. D. Dyer and D. J. Schrier, J. Med. Chem; 1992, 35, 3691 or EP-A-0446010 for 1,2,4-oxadiazoles and EP-A-0486798 for 1,3,4-oxadiazoles).
1,2,4-Thiadiazoles of the formula (III), where L is tosyl (p-tolylsulphonyl) may be obtained by the thermolysis of 5-substituted 1,3,4-oxathiazole-2-ones in excess p-tolylsulphonylnitrile conveniently in a hydrocarbon solvent, such as dodecane (see R. K. Howe and J. E. Franz, J. Org. Chem., 39, 962 (1974)). The 1,3,4-oxathiazolones can be prepared by reaction of acid amides with chlorocarbonylsulphenyl chloride by known procedures (see, for example, GB-A-1079348).
1,2,4-Thiadiazoles of the formula (III), where L is methylsulphonyl may be prepared by the reaction of methyl iodide followed by 3-chloroperoxybenzoic acid with 3-substituted-5-mercapto-1,2,4-thiazoles. The 5-mercapto-1,2,4-thiazoles can be prepared by the reaction of amidines with carbon disulphide and sulphur in the presence of sodium methoxide in methanol (see GB-A-1116198).
1,2,4-Oxadiazoles of the formula (III), where L is chloro, may be obtained by reacting 3-substituted 1,2,4-oxadiazol-5-ones with phosphoryl chloride. The 1,2,4-oxadiazolones can be prepared by acylation of amidoximes and cyclization of the resulting intermediate (see EP-A-0446010 or P. C. Unangst, G. P. Shrum, D. T. Connor, R. D. Dyer and D. J. Schrier, J. Med. Chem., 35, 3691 (1992)). Amidoximes are obtained by known methods, for example by the action of hydroxylamine on the appropriate nitriles.
Alternatively, the invention compounds of formula (I) may be prepared from a compound of the formula (IV), wherein L, M, X and n have the meanings given before and W is a group which can be converted by standard procedures described in the literature into the group BOC.C═A.OCH3. For example, where W is the group CH3 CO2 C.C═CH.OH, CH3 CO2 C.C═N.OH or CH3 NHOC.C═N.OH it may be converted to the appropriate group BOC.C═A.OCH3 by methylation with a compound CH3 L, wherein L is a leaving group such as halo or CH3 SO2.O, in the presence of a convenient base (such as sodium hydride or potassium carbonate). Where W is the phenylglyoxylic acid derivative, CO.CO2 CH3 or CO.CONHCH3, it may be converted to the appropriate group BOC.C═A.OCH3 by treatment with the Wittig reagent Ph3 P═CH.OCH3, wherein Ph is phenyl, or with methylhydroxylamine.
The compounds (IV) can be prepared by reacting a phenol of the general formula (IIa) with a thiadiazole or oxadiazole derivative of the general formula (III), as described above for the phenol (II). The phenol (IIa) can conveniently be prepared from appropriately substituted phenylacetic acid derivatives by methods known in the literature (see, for example, EP-A-0178826, EP-A-0254426, EP-A-0278595, EP-A-0299694 and EP-A-0398692).
The compounds of formula (I), wherein A is CH or N and B is NHCH3, can also be prepared from the corresponding compounds wherein A is CH or N and B is OH, by methods set out in the literature and in other ways described in EP-A-0398692.
In a further aspect the invention provides processes for preparing compounds of formula (I).
The compounds of formula (I) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae on rice and wheat and other Pyricularia spp. on other hosts; Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants; Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Septoria spp. (including Mycosphaerella graminicola and Leptosphaeria nodorum), Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals (e.g. wheat, barley, rye), turf and other hosts; Cercospora arachidicola and Cercosporidium personatum on peanuts and other Cercospora species on other hosts, for example, sugar beet, bananas, soya beans and rice; Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts and other Botrytis spp. on other hosts; Alternaria spp. on vegetables (e.g. cucumber), oil-seed rape, apples, tomatoes, cereals (e.g. wheat) and other hosts; Venturia spp. (including Venturia inaequalis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (e.g. wheat); Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat and other hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts; Aspergillus spp. and Aureobasidium spp. on wheat, lumber and other hosts; Ascochyta spp. on peas, wheat, barley and other hosts; Plasmopara viticola on vines; other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; Pythium spp. on turf and other hosts; Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; Thanatephorus cucumeris on rice and turf and other Rhizoctonia species on various hosts such as wheat and barley, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laetisaria fuciformis on turf; Mycosphaerella spp. on banana, peanut, citrus, pecan, papaya and other hosts; Diaporthe spp. on citrus, soybean, melon, pear, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Pyrenopeziza spp. on oil-seed rape and other hosts; Oncobasidium theobromae on cocoa causing vascular streak dieback; Fusarium spp., Typhula spp., Microdochium nivale, Ustilago spp., Urocystis spp., Tilletia spp., and Claviceps purpurea on a variety of hosts but particularly wheat, barley, turf and maize; Ramularia spp. on sugar beet and other hosts; post-harvest diseases particularly of fruit (e.g. Pencillium digitatum and P. italicum and Trichoderma viride on oranges, Colletotrichum musae and Gloesporium musarum on bananas and Botrytis cinerea on grapes); other pathogens on vines, notably Eutypa lata, Guignardia bidwellii, Phellinus igniarus, Phomopsis viticola, Pseudopezicula tracheiphila and Stereum hirsutum; other pathogens on lumber, notably Cephaloascus fragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp., Trichoderma pseudokoningii, Trichoderma viride Trichoderma harzianum, Aspergillus niger, Leptographium lindbergi and Aureobasidium pullulans; and fungal vectors of viral diseases e.g. Polymyxa graminis on cereals as the vector of barley yellow mosaic virus (BYMV).
Some of the compositions show a broad range of activities against fungi in vitro.
The compounds may move acropetally/locally in plant tissue. Moreover, the compounds may be volatile enough to be active in the vapour phase against fungi on the plant.
The invention therefore provides a method of combating fungi which comprises applying to a plant, to a seed of a plant or to the locus of the plant or seed a fungicidally effective amount of a compound as hereinbefore defined, or a composition containing the same.
The compounds may be used directly for agricultural purposes but are more conveniently formulated into compositions using a carrier or diluent. The invention thus provides fungicidal compositions comprising a compound as hereinbefore defined and an acceptable carrier or diluent therefor. It is preferred that all compositions, both solid and liquid formulations, comprise 0.0001 to 95%, more preferably 1 to 85%, for example 1 to 25% or 25 to 60%, of a compound as hereinbefore defined.
When applied the foliage of plants, the compounds of the invention are applied at rates of 0.1 g to 10 kg, preferably 1 g to 8 kg, more preferably 10 g to 4 kg, of active ingredient (invention compound) per hectare.
When used as seed dressings, the compounds of the invention are used at rates of 0.0001 g (for example 0.0001 g or 0.05 g) to 10 g, preferably 0.005 g to 8 g, more preferably 0.005 g to 4 g, of active ingredient (invention compound) per kilogram of seed.
The compounds can be applied in a number of ways. For example, they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules.
Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted, or to the soil generally, to paddy water or to hydroponic culture systems. The invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods or applied by land or aerial irrigation systems.
The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments.
The compounds are preferably used for agricultural and horticultural purposes in the form of a composition. The type of composition used in any instance will depend upon the particular purpose envisaged.
The fungicidal compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay. Such granules can be preformed granules suitable for application to the soil without further treatment. These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler. Compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrol-idone, propylene glycol or N,N-dimethylformamide). The compositions may also be in the form of water dispersible powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids. The powders and granules may also contain fillers and suspending agents.
The fungicidal compositions may also be in the form of soluble powders or granules, or in the form of solutions in polar solvents.
Soluble powders may be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank.
Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent. Suitable organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.
Aqueous suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included to stop the solid settling.
Fungicidal compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure of a propellant, e.g. fluorotrichloromethane or dichlorodifluoromethane.
The invention compounds can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.
Alternatively, the compounds may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
By including suitable additives, for example additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surface, the different compositions can be better adapted for various utilities. Other additives may be included to improve the biological efficacy of the various formulations. Such additives can be surface active materials to improve the setting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives, for example, certain mineral oil and natural plat oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.
The invention compounds can be used as mixtures with fertilisers (e.g. nitrogen-, potassium- or phosphorous-containing fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated with, a compound of formula (I) are preferred. Such granules suitably contain up to 25% by weight of the compound. The invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or metal complex thereof.
Water dispersible powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants, e.g. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.
Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethylammonium bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates).
Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, alkyl glucosides, polysaccharides and the lecithins and the condensation products of the said partial esters with ethylene oxide. Suitable suspending agents are hydrophilic colloids (for example, polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite.
Fungicidal compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use. Theses concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 95%, suitably 1-85%, for example 1-25% or 25-60%, by weight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0001 to 10%, for example 0.005 to 10%, by weight of active ingredient may be used.
The fungicidal compositions of this invention may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.
By including another fungicide, the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of general formula (I) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of fungicidal compounds which may be included in the composition of the invention are (RS)-1-aminopropylphosphonic acid, (RS)-4-(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-yl-methyl)butyronitrile, (Z)-N-but-2-enyloxmethyl-2-chloro-2',6'-diethylacetanilide, 1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 4-(2,2-difluoro-1,3-benzodioxol-4-yl)pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylobenzimidazole-1-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxol-(4,5-g)quinoline-7-carboxylic acid, α-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-γ-butyrolactone, N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, BAS 490F, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, chinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprodinyl, cyprofuram, debacarb, di-2-pyridyl disulphide 1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine, dicloran, didecyl dimethyl ammonium chloride, diethofencarb, difenoconazole, O,O-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, didemorph, dodine, doguadine, edifenphos, epoxiconazole, etaconazole, ethirimol, ethoxyquin, ethyl (Z)-N-benzyl-N-([methyl(methylthioethylideneamino-oxycarbonyl)amino]thio)-β-alaninate, etridiazole, fenaminosulph, fenapanil, fenarimol, fenbucnazole, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furametpyr, furalaxyl, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, ICIA5504, imazalil, imibenconazole, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxzyl, metconazole, methfuroxam, metiram, metiram-zinc, metsulfovax, myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinconazole, quinomethionate, quintozene, rabenazole, sodium pentachlorophenate, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamine, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triacetate salt of 1,1'-iminodi(octamethylene)diguanidine, triadimefon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb and ziram. The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
The compounds of formula (I) may also be used to combat and control infestations of insect pests and also other invertebrate pests, for example, acarine pests. The insect and acarine pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, forestry, the storage or products of vegetable origin, such as fruit, grain and timber, and also those pests associated with the transmission of diseases of man and animals.
In order to apply the compounds to the locus of the pests they are usually formulated into compositions which include in addition to the insecticidally active ingredient or ingredients of formula I suitable inert diluent or carrier materials, and/or surface active agents. The insecticidal compositions may also comprise another pesticidal material, for example another insecticide or acaricide, or a fungicide, or may also comprise an insecticide synergist, such as for example didecyl imidazole, safroxan, or piperonyl butoxide.
The insecticidal compositions may be in the form of dusting powders wherein the active ingredient is mixed with a solid diluent or carrier, for example kaolin, bentonite, kieselguhr, or talc, or they may be in the form of granules, wherein the active ingredient is absorbed in a porous granular material for example pumice.
Alternatively the insecticidal composition may be in the form of baits wherein the active ingredient is mixed with a nutrient carrier for example sucrose, yeast, malt extract, cereal or cereal products and optionally an attractant such as a pheromone or pheromone analogue.
Alternatively the insecticidal compositions may be in the form of liquid preparations to be used as dips or sprays, which are generally aqueous dispersions or emulsions of the active ingredient in the presence of one or more known wetting agents, dispersing agents or emulsifying agents (surface active agents) of the type described above of for the fungicidal compositions.
The insecticidal compositions may be prepared by dissolving the active ingredient in a suitable solvent, for example, a ketonic solvent such as diacetone alcohol, or a aromatic solvent such as trimethylbenzene and adding the mixture so obtained to water which may contain one or more known wetting, dispersing or emulsifying agents.
Other suitable organic solvents are dimethyl formamide, ethylene dichloride, isopropyl alcohol, propylene glycol and other glycols, diacetone alcohol, toluene, kerosene, white oil, methylnaphthalene, xylenes and trichloroethylene, N-methyl-2-pyrrolidone and tetrahydrofurfuryl alcohol (THFA).
The insecticidal compositions which are to be used in the form of aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient or ingredients, the said concentrate to be diluted with water before use. These concentrates are often required to withstand storage for prolonged periods and after such storage, to be capable of dilution with water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may contain 10-85% by weight of the active ingredient or ingredients. When diluted to form aqueous preparations such preparations may contain varying amounts of the active ingredients depending upon the purpose for which they are to be used. For agricultural or horticultural purposes, an aqueous preparation containing between 0.0001% and 0.1% by weight of the active ingredient (approximately equivalent to from 5-2000 g/ha) is particularly useful.
In use the insecticidal compositions are applied to the pests, to the locus of the pests, to the habitat of the pests, to growing plants liable to infestation by the pests, or, where there is systemic uptake by plants, to the soil surrounding plants liable to infestation, by any of the known means of applying pesticidal compositions, for example, by dusting or spraying.
The compounds of the invention may be the sole active ingredient of the insecticidal composition or they may be admixed with one or more additional active ingredients such as insecticides, insecticide synergists, herbicides, fungicides or plant growth regulators where appropriate. Suitable additional active ingredients for inclusion in admixture with the compounds of the invention may be compounds which will broaden the spectrum of activity of the compounds of the invention or increase their persistence in the location of the pest. They may synergise the activity of the compound of the invention of complement the activity for example by increasing the speed of effect, improving knockdown or overcoming repellency. Additionally multi-component mixtures of this type may help to overcome or prevent the development of resistance to individual components.
The particular insecticide, herbicide or fungicide included in the mixture will depend upon its intended utility and the type of complementary action required. Examples of suitable insecticides include the following:
a) Pyrethroids such as permethrin, esfenvalerate, deltamethrin, cyhalothrin in particular lambda-cyhalothrin, cypermethrin, alpha cypermethrin, bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids for example ethofenprox, natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin, or 5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl) cyclopropane carboxylate;
b) Organophosphates such as profenofos, sulprofos, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chloropyrifos, phosalone, fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl, fenitrothion or diazinon;
c) Carbamates (including aryl carbamates) such as pirimicarb, cloethocarb, carbofuran, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur or oxamyl;
d) Benzoyl ureas such as triflumuron, or chlorfluazuron;
e) Organic tin compounds such as cyhexatin, fenbutatin oxide, or azocyclotin;
f) Macrolides such as avermectins or milbemycins, for example such as abamectin, ivermectin, and milbemycin;
g) Hormones such as pheromones;
h) Organochlorine compounds such as benzene hexachloride, DDT, chlordane or dieldrin.
i) Amidines, such as chlordimeform or amitraz.
In addition to the major chemical classes of insecticide listed above, other insecticides having particular targets may be employed in the mixture if appropriate for the intended utility of the mixture. For instance selective insecticides for particular crops, for example stemborer specific insecticides for use in rice such as cartap or buprofezin can be employed. Alternatively insecticides specific for particular insect species/stages for example ovo-larvicides such as clofentezine, flubenzimine, hexythiazox and tetradifon, acaricides such as dicofol, propargite, bromopropylate, chlorobenzilate, or growth regulators such as hydramethylnon, cyromazine, methoprene, hydroprene, chlorfluazuron and diflubenzuron may also be included in the compositions.
Examples of suitable insecticide synergists for use in the compositions include piperonyl butoxide, sesamex, and dodecyl imidazole.
Suitable herbicides, fungicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required. An example of a rice selective herbicide which can be included is propanil, an example of a plant growth regulator for use in cotton is "Pix", and examples of fungicides for use in rice include blasticides such as blasticidin-S.
The ratio of the compound of the invention to the other active ingredient in the composition will depend upon a number of factors including type of target, effect required from the mixture etc.
However in general, the additional active ingredient of the composition will be applied at about the rate as it is usually employed, or at a slightly lower rate if synergism occurs.
The compounds of formula I and insecticidal compositions comprising them have shown themselves active against a variety of insect and other invertebrate pests. They are particularly useful in controlling sucking pests such as aphids and mites. Compounds of the present invention are also generally characterised by a relatively broad spectrum of activity which may include Lepidoptera and Coleoptera in addition to public health pests such as flies and cockroaches.
They may also be active against organophosphate, pyrethroid or cyclodiene (for example lindane or dieldrin) resistant strains of public and animal health pests. They may be effective in combating both susceptible and resistant strains of the pests in their adult and immature stages of growth, and may be applied to the infested host animal by topical, oral or parenteral administration.
The following Examples illustrate the invention. Throughout the Examples, the term `ether` refers to diethyl ether, magnesium sulphate was used to dry solutions except where otherwise indicated, and solutions were concentrated under reduced pressure. All reactions were performed under an atmosphere of nitrogen and solvents were dried before use, where appropriate. Unless otherwise stated, chromatography was performed on a column of silica gel as the stationary phase. Where shown, infrared and NMR data are selective; no attempt is made to list every absorption in all cases. 1 H NMR spectra were recorded using CDCl3 -solutions unless otherwise stated. The following abbreviations are used throughout:
NMR=nuclear magnetic resonance
m=multiplet
mp=melting point
ppm=parts per million
s=singlet
DMF=N,N-dimethylformamide
EXAMPLE 1
This Example illustrates the preparation of (E)-methyl 2-(2-[3-(3-trifluoromethylphenyl)-1,2,4-thiadiazol-5-yloxy]phenyl)-3-methoxyacrylate (Compound 32 of Table 1).
(E)-Methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.26 g; prepared as described in Example 3 of EP-A-0242081) and 5-chloro-3[3-trifluoromethylphenyl]-1,2,4-thiadiazole (0.8 g) were dissolved in DMF (10 ml) at 5° C. Potassium carbonate (0.836 g) was then added and the reaction mixture stirred at room temperature for 48 hours. Water and ether were added and the organic layer separated. Any residual product in the aqueous layer was extracted (twice) with ether and the combined ether layers washed with brine before drying (anhydrous sodium sulphate) and concentrating to give an oil. Column chromatography (twice; firstly with 80% dichloromethane in hexane and then with 1:1 ether/hexane) gave the title product as an orange gum (0.86 g, 66%); 1 H NMR (CDCl3, 270 MHz): δ3.6(s,3H), 3.85(s,3H), 7.58(s,1H), 7.35-7.75(m,6H), 8.35-8.50(m,2H) ppm.
EXAMPLE 2
This Example illustrates the preparation of (E)-methyl 2-(2-[3-(3-methylbenzyl)-1,2,4-thiadiazol-5-yloxy]phenyl)-3-methoxyacrylate (Compound 26 of Table 9).
(E)-Methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.48 g; prepared as described in Example 3 of EP-A-0242081) and 5-chloro-3-(3-methylbenzyl)-1,2,4-thiadiazole (0.8 g) were dissolved in DMF (10 ml) and cooled to 5° C. Potassium carbonate (0.98 g) was then added and the reaction mixture stirred for 96 hours at room temperature. Further potassium carbonate (0.5 g) was added and the reaction mixture stirred for a further 24 hours. Water and ether were added and the layers separated. Any residual product was extracted from the aqueous layer with ether (twice) and the combined organic layers washed with brine. After drying (anhydrous sodium sulphate) the solvent was removed under reduced pressure to give an oil. Column chromatography (twice; firstly with 10% ether/90% dichloromethane and then with 60% ether/40% hexane) gave the title product as a gum (117 mg, 8%); 1 H NMR (CDCl3, 270 MHz): δ2.32(s,3H), 3.58(s,3H), 3.65(s,3H), 4.1(s,2H), 7.5(s,1H), 7.0-7.45(m,8H) ppm.
EXAMPLE 3
This Example illustrates the preparation of (E)-methyl 2-(2-[5-phenyl-1,3,4-thiadiazol-2-yloxy]phenyl)-3-methoxyacrylate (Compound 1 Table 5).
2-Methylsulphonyl-5-phenyl-1,3,4-thiadiazole (1.11 g) and potassium carbonate (0.95 g) were stirred in DMF (20 ml) and cooled to 5° C. A solution of (E)-methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.43 g; prepared as described in Example 3 of EP-A-0242081) in DMF (10 ml) was added over 2 minutes and the reaction mixture stirred for 1/2 hour at 0° C. in a cooling bath. The cooling bath was removed and the reaction stirred for 41/2 days.
The reaction mixture was poured into water and the product extracted with ether (three times). The ether layers were washed twice with aqueous sodium hydroxide solution then 3 times with water before drying and concentrating to give a yellow solid. Column chromatography (twice, using 2:1 ether/hexane as eluent) gave the title product as a yellow gum (0.24 g, 14%); 1 H NMR (CDCl3, 270 MHz): δ7.80-7.86(m,2H), 7.58(s,1H), 7.3-7.48(m,7H), 3.79(s,3H), 3.65(s,3H) ppm.
EXAMPLE 4
This Example illustrates the preparation of (E)-methyl 2-(2-[3-(2-pyrazinyl)-1,2,4-thiadiazol-5-yloxy]phenyl)-3-methoxyacrylate (Compound 191 of Table 1).
(E)-Methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.28 g; prepared as described in Example 3 of EP-A-0242081) and 5-chloro-3-(2-pyrazinyl)-1,2,4-thiadiazole (0.61 g) were dissolved in DMF (10 ml) at room temperature. Potassium carbonate (0.85 g) was added and the reaction mixture stirred for 25 hours. Water was added and the product extracted with ether (4 times). The combined organic phases were washed with brine, dried and concentrated to give an oil.
Column chromatography (60% ethyl acetate/40% dichloromethane) on silica gel gave the title product as a yellow gum (0.816 g, 75%); 1 H NMR (CDCl3, 270 MHz): δ3.65(s,3H), 3.8(s,3H), 7.4(m,4H), 7.57(s,1H), 8.7(m,2H), 9.45(S,1H) ppm.
EXAMPLE 5
This Example illustrates the preparation of (E)-methyl 2-(2-[3-(2-thienyl)-1,2,4-thiadiazol-5-yloxy]phenyl)-3-methoxy acrylate (compound 180 of Table 1).
5-Chloro-3-(2-thienyl)-1,2,4-thiadiazole (0.6 g) was dissolved in DMF (10 ml) and (E)-methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.23 g; prepared as described in Example 3 of EP-A-0242081) was added followed by potassium carbonate (0.818 g). The reaction mixture was stirred at room temperature for 48 hours and then diluted with water. Extraction three times with ether, drying and concentration gave an oil.
Column chromatography (firstly with 50/50 ether/hexane, then repeated with dichloromethane) gave the title product as a colourless gum (0.369 g, 33%); 1 H NMR (CDCl3, 270 MHz): δ3.62(s,3H), 3.77(s,3H), 7.1(m,1H), 7.4(m,5H), 7.57(s,1H), 7.8(m,1H) ppm.
EXAMPLE 6
This Example illustrates the preparation of (E)-methyl 2-(2-[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yloxy]phenyl)-3-methoxyacrylate (Compound No. 7 of Table 5').
Potassium carbonate (0.76 g) was added in one portion to a solution of (E)-methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.14 g; prepared as described in Example 3 of EP-A-0242081) in DMF (20 ml) kept at 5° C. in a cooling bath. A solution of 2-methylsulphonyl-5-(4-chlorophenyl)-1,3,4-oxadiazole in DMF (15 ml) was added dropwise during 15 minutes. The cooling bath was removed and the reaction mixture stirred for 21/2 hours before leaving to stand overnight.
The solution was poured into water and the organic material extracted with ether three times.
The ether layer was dried before concentrating to a yellow solid. Trituration with ether gave the title product as a pure white solid (1.36 g, 70%); m.p 109°-111° C.
EXAMPLE 7
This Example illustrates the preparation of (E)-methyl 2-(2-[3-(2-chlorophenyl)-1,2,4-thiadiazol-5-yloxy]phenyl)-3-methoxyacrylate (compound 5 of Table 1).
5-(4-Methylphenylsulphonyl)-3-(2-chlorophenyl)-1,2,4-thiadiazole (1.43 g) was dissolved in DMF (25 ml) and (E)-methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.69 g) was added. The solution was cooled to 5° C. before potassium carbonate (1.12 g) was added and the reaction stirred for 45 minutes at 5° C. After stirring at room temperature for 22 hours the reaction mixture was poured into water and extracted with ether. The solvent was dried and concentrated to give a tacky yellow solid. Column chromatography (eluting with dichloromethane) gave a yellow solid which, upon trituration with hexane, gave the pure product (0.86 g, 52%); mp 127°-129° C.
EXAMPLE 8
This Example illustrates the preparation of (E)-methyl 2-(2-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yloxy]phenyl)-3-methoxyacrylate (compound 2 Table 1').
(E)-Methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.45 g) was dissolved in DMF (10 ml) and cooled to 5° C. Potassium carbonate (0.97 g) was added followed by 5-chloro-3-(2-fluorophenyl)-1,2,4-oxadiazole (1.32 g) in DMF (15 ml). The resulting mixture was stirred at room temperature for 4 hours and then poured into water. The product was extracted into ether and the solution dried and concentrated to give a yellow gum. Trituration with ether and filtration gave the product as an off-white solid (1.82 g, 74%); mp 90°-92° C.
EXAMPLE 9
The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows.
The plants were grown in John Innes Potting Compost (No 1 or 2) in 4 cm diameter minipots. The test compounds were formulated either by bead milling with aqueous Dispersol T or as a solution in acetone or acetone/ethanol which was diluted to the required concentration immediately before use. The formulations (100 ppm active ingredient) were sprayed on to the foliage or applied to the roots of the plants in the soil. The sprays were applied to maximum retention and the root drenches to a final concentration equivalent to approximately 40 ppm a.i. in dry soil. Tween 20 was added to give a final concentration of 0.05% when the sprays were applied to cereals.
For most of the tests the compounds were applied to the soil (roots) or to the foliage (by spraying) one or two days before the plant was inoculated with the disease. An exception was the test on Erysiphe graminis in which the plants were inoculated 24 hours before treatment. Foliar pathogens were applied by spray as zoosporangial suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to fourteen days according to the disease and environment.
The disease level present (i.e. leaf area covered by actively sporulating disease) on each of the treated plants was recorded using the following assessment scale:
0=0% disease present
1=0.1-1% disease present
3=1.1-3% disease present
5=3.1-5% disease present
10=5.1-10% disease present
20=10.1-20% disease present
30=20.1-30% disease present
60=30.1-60% disease present
90=60.1-100% disease present
Each assessment was then expressed as a percentage of the level of disease present on the untreated control plants. This calculated value is referred to as a POCO (Percentage of Control) value. An example of a typical calculation is as follows:
Disease level on untreated control=90
Disease level on treated plant=30 ##EQU1##
This calculated POCO value is then rounded to the nearest of the values in the 9-point assessment scale shown above. In this particular example, the POCO value would be rounded to 30. If the calculated POCO falls exactly mid-way between two of the points, it is rounded to the lower of the two values.
The results are shown in Table 18.
              TABLE 18                                                    
______________________________________                                    
Compound                                                                  
No of                                                                     
(Table No)                                                                
         Pr     Egt    Sn   Po   Tc   Vi   Pv   Pil                       
______________________________________                                    
1(1)     0      0      0    --   5    0    --   0                         
1(1')    0      0      0    10   30   0    0    0                         
1(5)     0      30     0    0    90   0    0    0                         
1(5')    0      0      0    0    0    0    --   0                         
1(13')   0      --     0    --   90   0    0    0                         
2(1)     0      1      0    0    0    0    0    0                         
2(1')    3      30     5    --   --   0    0    0                         
2(5')    0      0      90   --   5    0    0    0                         
3(1)     --     0      0    --   0    0    0    0                         
3(2)     0      3      --   0    30   0    0    0                         
3(4)     0.sup.b                                                          
                0.sup.b                                                   
                       --   0.sup.b                                       
                                 0.sup.b                                  
                                      0.sup.b                             
                                           0.sup.b                        
                                                10.sup.b                  
3(5')    0      0      0    --   90   0    0    0                         
4(1)     --     0      0    --   0    0    0    0                         
4(5')    0      90     0    --   30   0    0    0                         
5(1)     90     60     0    0    0    0    0    30                        
5(5')    0      0      5    60   0    --   0    0                         
6(1)     --     0      0    --   0    0    0    0                         
6(5')    5      90     0    --   --   0    0    0                         
7(1)     --     0      0    0    0    0    0    0                         
7(1')    0      0      0    0    5    0    0    0                         
7(2)     30     0      0    --   0    0    0    0                         
7(4)     0      0      0    --   0    --   0    90                        
7(5')    0      0      0    0    0    0    0    60                        
8(1)     90.sup.a                                                         
                10.sup.a                                                  
                       0.sup.a                                            
                            0.sup.a                                       
                                 90.sup.a                                 
                                      10.sup.a                            
                                           0.sup.a                        
                                                90.sup.a                  
9(1)     0      0      0    0    0    0    0    10                        
9(5')    60     30     0    30   --   0    0    0                         
10(5')   0      0      0    10   0    --   0    0                         
17(1)    0      1      0    --   5    0    0    30                        
25(1)    5      0      0    0    0    --   0    0                         
25(5')   0      20     0    60   0    0    0    0                         
26(1)    0      0      0    0    0    0    0    0                         
26(5')   0      10     0    5    --   0    0    0                         
26(9)    90.sup.a                                                         
                60.sup.a                                                  
                       90.sup.a                                           
                            60.sup.a                                      
                                 90 .sup.a                                
                                      0.sup.a                             
                                           0.sup.a                        
                                                10.sup.a                  
27(5')   0      0      0    0    0    0    0    0                         
31(1)    0      90     0    --   0    0    0    0                         
32(1)    0      0      0    --   0    0    0    30                        
32(1')   0      0      0    5    --   0    0    0                         
32(2)    60     20     --   --   20   0    0    30                        
32(5)    0      0      0    --   0    0    0    10                        
32(5')   0      10     20   0    0    0    --   30                        
33(1)    10     --     0    --   0    0    0    0                         
33(5')   0      0      0    0    0    0    0    0                         
35(1)    0      0      0    0    0    0    0    0                         
35(5')   20     60     0    0    20   0    0    3                         
36(1)    0      0      0    0    --   0    0    0                         
36(5')   0      0      0    --   --   0    0    0                         
38(2)    --     90.sup.b                                                  
                       60.sup.b                                           
                            5.sup.b                                       
                                 0.sup.b                                  
                                      0.sup.b                             
                                           0.sup.b                        
                                                90.sup.b                  
38(4)    --     0      0    0    0    0    0    90                        
41(1)    0      1      0    0    0    0    0    0                         
44(1)    --     0      0    --   0    0    0    1                         
44(5')   0      60     3    0    5    10   0    0                         
45(1)    0      0      0    0    0    0    0    0                         
45(5)    90     90     0    60   90   0    0    90                        
45(5')   10     20     3    20   5    10   0    5                         
46(5')   30     10     60   0    90   0    0    0                         
47(1)    --     0      0    0    0    0    0    0                         
47(5')   90     90     0    20   90   0    0    0                         
48(1)    10     0      0    0    60   0    0    0                         
48(5')   90     30     0    1    30   0    0    0                         
176(5')  0      0      0    10   0    0    0    1                         
178(1)   90.sup.a                                                         
                90.sup.a                                                  
                       20.sup.a                                           
                            0.sup.a                                       
                                 90 .sup.a                                
                                      0.sup.a                             
                                           0.sup.a                        
                                                5.sup.a                   
180(1)   30     30     0    0    0    0    0    0                         
180(5')  0      0      0    10   60   0    0    0                         
181(1)   0      0      0    0    0    0    0    3                         
181(5')  --     0      0    --   90   0    0    0                         
183(1)   --     --     90   --   90   0    30   20                        
184(5)   60     20     5    --   60   0    0    1                         
919(1)   0      0      0    0    30   0    0    0                         
193(5')  90     30     0    0    60   0    0    0                         
198(1)   --     0      0    --   0    0    0    0                         
213(1)   --     0      0    --   0    0    0    1                         
214(1)   --     0.sup.a                                                   
                       30.sup.a                                           
                            0.sup.a                                       
                                 --   0.sup.a                             
                                           30.sup.a                       
                                                90.sup.a                  
229(1)   0      0      0    0    0    0    0    5                         
234(5')  0      30     0    30   0    0    0    20                        
235(1)   0      0      10   0    0    0    0    -                         
235(5')  0      0      --   0    0    --   0    0                         
236(1)   0      30     --   0    0    0    0    -                         
236(5')  0      0      --   0    5    0    0    -                         
237(5')  0      0      0    --   5    0    0    0                         
237(13') 0      90     0    --   60   0    0    0                         
244(5')  5      90     --   5    3    0    0    0                         
246(13') 20.sup.a                                                         
                90.sup.a                                                  
                       90.sup.a                                           
                            30.sup.a                                      
                                 90.sup.a                                 
                                      0.sup.a                             
                                           0.sup.a                        
                                                0.sup.a                   
246(14') 90.sup.b                                                         
                90.sup.b                                                  
                       90.sup.b                                           
                            0.sup.b                                       
                                 90.sup.b                                 
                                      0.sup.b                             
                                           0.sup.b                        
                                                0.sup.b                   
246(16') 90.sup.b                                                         
                90.sup.b                                                  
                       90.sup.b                                           
                            60.sup.b                                      
                                 90.sup.b                                 
                                      10.sup.b                            
                                           90.sup.b                       
                                                90.sup.b                  
247(1)   0      0      --   --   0    0    0    0                         
247(5')  1.sup.a                                                          
                90.sup.a                                                  
                       0.sup.a                                            
                            --   60.sup.a                                 
                                      0.sup.a                             
                                           0.sup.a                        
                                                0.sup.a                   
258(5')  90.sup.a                                                         
                90.sup.a                                                  
                       90.sup.a                                           
                            90.sup.a                                      
                                 90.sup.a                                 
                                      0.sup.a                             
                                           0.sup.a                        
                                                -                         
270(1)   0      0      --   --   0    0    0    0                         
270(5')  0      90     --   20   0    0    0    0                         
277(1)   60     90     --   --   0    0    0    3                         
278(13') 0      90     --   90   90   3    0    90                        
______________________________________
Unless stated otherwise, data represent activity following application as a combined foliar spray and root drench treatment at 100 ppm.
a 10 ppm foliar application only
a 25 ppm foliar application only
No result
Key to Diseases
Pr Puccinia recondita
Egt Erysiphe graminis tritici
Sn Septoria nodorum
Po Pyricularia oryzae
Tc Thanetophorus cucumeris
Vi Venturia inaequalis
Pv Plasmopara viticola
Pil Phytophthora infestans lycopersici
EXAMPLE 10
The activity of the compounds of formula (I) was determined using a variety of pests. The pests were treated with a liquid composition containing 250 parts per million (ppm) by weight of the compound except in the case of Meloidogyne incognita, which was treated with a liquid composition containing 6.25 ppm by weight of the compound in an in vitro test. The compositions were made by dissolving the compound in acetone and ethanol (50:50) mixture and diluting the solutions with water containing 0.1% by weight of a wetting agent sold under the trade name "SYNPERONIC" NP8 (further diluting to 6.25 ppm in the case of Meloidogyne incognita) until the liquid composition contained the required concentration of the compound. "SYNPERONIC" is a Registered Trade Mark.
The test procedure adopted with regard to each pest was basically the same and comprised supporting a number of the pests on a medium which was usually a substrate, a host plant or a foodstuff on which the pests feed, and treating either or both the medium and the pests with the compositions. The mortality of the pests was then assessed at periods usually varying from two to five days after the treatment with the exception of Musca domestica, for which an additional initial knockdown assessment was made.
The results of the tests are presented in Table 19 for each of the compounds. The results indicate a grading of mortality (or knockdown in the case of Musca domestica), designated as A, B or C wherein A indicates 80-100% mortality, B indicates 40-79% mortality and C indicates 0-39% mortality. The pest species is designated by a letter code.
Information regarding the pest species, the support medium or food, and the type and duration of the test is given in Table 20.
              TABLE 19                                                    
______________________________________                                    
Compound                                                                  
        Tu      Mp     Md     Hv   Se   Db   Mi                           
No.     initial                                                           
(Table No)                                                                
        knockdown/kill                                                    
______________________________________                                    
1(1)    A       A      A/A    C    C    A    C                            
1(1')   C       C      B/C    C    C    C    C                            
1(5)    C       C      A/C    C    C    C    C                            
1(5')   B       A      B/C    C    C    A    C                            
1(13')  B       C      A/A    C    C    B    C                            
2(1)    C       A      A/A    C    C    A    C                            
2(1')   A       B      A/A    C    C    C    C                            
2(5')   C       C      A/A    C    C    B    --                           
3(1)    A       A      A/A    C    C    C    C                            
3(2)    A       C      A/B    C    C    C    --                           
3(4)    A       C      B/B    C    C    C    --                           
3(5')   A       A      A/A    C    C    A    C                            
4(1)    A       A      A/B    C    C    B    C                            
4(5')   A       C      A/A    C    A    A    --                           
5(1)    C       C      --/--  C    C    C    C                            
5(5')   C       C      C/B    C    C    A    C                            
6(1)    A       A      A/A    C    C    C    C                            
6(5')   A       A      B/--   C    C    C    C                            
7(1)    A       A      A/A    C    B    A    C                            
7(1')   C       A      A/A    C    C    B    C                            
7(2)    A       A      A/A    C    C    B    C                            
7(4)    B       A      B/A    C    C    C    C                            
7(5')   A       A      A/A    B    A    A    B                            
9(1)    A       A      CIA    C    C    B    C                            
9(5')   A       A      A/C    C    C    B    C                            
10(5')  C       A      A/A    C    A    A    C                            
17(1)   B       A      A/C    C    C    C    B                            
25(1)   B       B      C/B    C    C    C    C                            
25(5')  A       C      C/C    C    C    C    C                            
26(1)   A       A      A/A    C    C    C    C                            
26(5')  B       B      C/C    C    C    B    C                            
26(9)   B       A      A/A    C    C    C    C                            
27(1)   C       B      C/A    C    C    C    C                            
27(5')  A       A      C/C    C    C    C    C                            
31(1)   A       A      A/B    B    C    C    C                            
32(1)   A       C      A/A    C    A    C    C                            
32(1')  A       A      A/C    C    C    C    C                            
32(2)   B       A      A/B    C    C    A    C                            
32(5)   C       A      A/A    C    C    C    C                            
32(5')  C       A      B/A    C    C    C    C                            
33(1)   A       A      A/A    A    A    A    C                            
33(5')  A       A      C/A    A    A    A    C                            
35(1)   C       A      C/B    C    C    C    C                            
35(5')  A       B      C/C    C    C    C    C                            
36(1)   A       A      A/C    C    C    A    C                            
36(5')  B       A      C/C    C    C    B    C                            
38(1)   A       A      --/A   C    C    A    C                            
38(2)   C       A      A/A    C    C    A    B                            
38(4)   A       A      A/A    C    C    A    C                            
41(1)   A       A      A/A    C    C    C    C                            
44(1)   A       A      C/A    C    C    C    C                            
44(5')  C       B      B/B    C    B    C    C                            
45(1)   C       A      A/A    C    B    B    --                           
45(5')  C       C      A/B    C    B    C    C                            
46(5')  A       C      ciC    C    C    A    --                           
47(1)   A       A      A/A    C    C    A    C                            
47(5')  C       C      C/C    C    C    C    C                            
48(1)   C       C      C/C    C    C    C    C                            
48(5')  C       B      C/A    C    C    A    C                            
176(5') A       A      B/B    C    C    A    C                            
180(1)  B       B      C/C    C    --   C    C                            
180(5') B       C      --/--  C    C    C    C                            
181(1)  C       C      B/C    C    C    C    C                            
181(5') B       C      C/C    C    C    C    C                            
183(1)  B       C      C/C    C    C    C    C                            
184(5)  C       C      C/C    C    C    C    C                            
191(1)  C       C      C/C    C    C    C    C                            
193(5') C       C      C/C    C    C    C                                 
198(1)  C       A      A/A    C    C    C    C                            
213(1)  C       C      C/C    C    C    C    C                            
214(1)  B       C      B/C    C    C    C    C                            
229(1)  C       B      B/C    C    --   C    C                            
234(5') A       A      C/C    A    C    C    C                            
235(1)  A       A      --/A   C    C    A    C                            
235(5') C       B      A/A    C    C    C    C                            
236(1)  A       A      A/A    C    C    A    C                            
236(5') A       A      A/A    B    C    A    C                            
237(5') A       A      C/A    C    C    A    C                            
237(13')                                                                  
        A       B      A/A    C    C    B    C                            
244(5' )                                                                  
        A       A      B/B    C    C    A    C                            
246(13')                                                                  
        A       C      A/A    C    C    C    C                            
246(14) A       A      A/B    C    C    C    C                            
247(1)  A       A      A/A    B    C    A    C                            
247(5') C       A      A/A    C    C    A    C                            
258(5') A       A      --/A   C    C    A    C                            
270(1)  C       B      C/C    C    C    C    C                            
270(5') C       B      B/A    C    C    B    C                            
277(1)  A       A      C/B    C    C    B    C                            
278(13')                                                                  
        C       C      C/C    C    C    C    --                           
______________________________________                                    
 --No result                                                              

                                  TABLE 20                                
__________________________________________________________________________
CODE LETTERS          SUPPORT/  TYPE OF                                   
                                       DURATION                           
(TABLE 18)                                                                
          TEST SPECIES                                                    
                      MEDIUM/FOOD                                         
                                TEST   (DAYS)                             
__________________________________________________________________________
Tu        Tetranychus urticae                                             
                      French bean                                         
                                Contact                                   
                                       3                                  
          (spider mite)                                                   
                      leaf                                                
Mp        Myzus persicae                                                  
                      Chinese   Contact                                   
                                       3                                  
          (aphid)     Cabbage leaf                                        
Md        Musca domestica                                                 
                      Cotton wool/                                        
                                Contact                                   
                                       2                                  
          (housefly-adult)                                                
                      sugar     Knockdown                                 
                                       15 min                             
Hv        Heliothis virescens                                             
                      Soya leaf Residual                                  
                                       5                                  
          (tobacco budwom)                                                
Se        Spodoptera exigua                                               
                      Cotton leaf                                         
                                Residual                                  
                                       5                                  
          (lesser armyworm-larva)                                         
Db        Diabrotica balteata                                             
                      Filter paper/                                       
                                Residual                                  
                                       2                                  
          (cucumber beetle-larva)                                         
                      maize seed                                          
Mi        Meloidogyne incognita                                           
                      in vitro  Contact                                   
                                       2                                  
          (rootknot nematode-larva)                                       
__________________________________________________________________________
 "Contact" test indicates that both pests and medium were treated,        
 "Residual" indicates that the medium was treated before infestation with 
 the pests and "in vitro" indicates that the pest was suspended in an     
 aqueous medium containing the treatment.
"Contact" test indicates that both pests and medium were treated, "Residual" indicates that the medium was treated before infestation with the pests and "in vitro" indicates that the pest was suspended in an aqueous medium containing the treatment. ##STR2##

Claims (11)

I claim:
1. A compound having the general formula (I):
or a stereoisomer thereof, wherein A is CH or N; B is OCH3 or NHCH3 ; one of L and M is N and the other is S or O; n is 0 or 1; and X is an optionally substituted carbocyclic or heterocyclic group selected from phenyl, naphthyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, indolinyl, isoindolinyl, benzofuranyl, benzothiophenyl, benzimidazolinyl, benzoxazolyl, benzthiazolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbomanyl, adamantyl, cyclopentenyl, cycloheptenyl, cyclooctenyl, cyclohexenyl, norbomenyl, oxiranyl, aziridinyl, azetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl and morpholino, the carbocyclic or heterocyclic group being optionally substituted with one or more of the following: halo, hydroxy, mercapto, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C2-4 alkenyloxy, C2-4 alkynyloxy, halo(C1-4)alkyl, halo(C1-4)alkoxy, C1-4 alkylthio, hydroxy(C1-4)alkyl, C1-4 alkoxy(C1-4)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, methylenedioxy or ethylenedioxy in which the methylene or ethylene group is optionally substituted with fluorine or C1-4 alkyl, phenyl, pyridyl, pyrimidinyl, phenoxy, pyridyloxy, pyrimidinyloxy, phenyl(C1-4)alkyl in which the alkyl moiety is optionally substituted with hydroxy, pyridyl(C1-4)alkyl, pyrimidinyl(C1-4)alkyl, phenyl(C2-4)alkenyl, pyridyl(C2-4)alkenyl, pyrimidinyl(C2-4)alkenyl, phenyl(C1-4)alkoxy, pyridyl(C1-4)alkoxy, pyrimidinyl(C1-4)alkoxy, phenoxy(C1-4)alkyl, pyridyloxy(C1-4)alkyl, pyrimidinyloxy(C1-4)alkyl, C1-4 alkanoyloxy, benzoyloxy, cyano, thiocyanato, nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --OSO2 R", --SO2 R', --COR', --CR'═NR" or --N═CR'R" in which R' and R" are independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C1-4 alkyl or C1-4 alkoxy, and the phenyl, pyridyl and pyrimidinyl rings of any of the foregoing substitutents other than R' and R" being optionally substituted with one or more of the following: halo, hydroxy, mercapto, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C2-4 alkenyloxy, C2-4 alkynyloxy, halo(C1-4)alkyl, halo(C1-4)alkoxy, C1-4 alkylthio, hydroxy(C1-4)alkyl, C1-4 alkoxy(C1-4)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, alkanoyloxy, benzoyloxy, cyano, thiocyanato, nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --OSO2 R", --SO2 R', --COR', --CR'═NR" or --N═CR'R" in which R' and R" have the meanings given above.
2. A compound according to claim 1 wherein A is CH or N; B is OCH3 ; one of L and M is N and the other is S or O; X is phenyl optionally substituted with halo, C1-4 alkyl, halo(C1-4)alkyl, C1-4 alkoxy, halo(C1-4)alkoxy, C1-4 alkoxy(C1-4)alkyl, methylenedioxy, ethylenedioxy, cyano, nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --COR', --SO2 R' or --OSO2 R' in which R' and R" are independently hydrogen or C1-4 alkyl; and n is 0 or 1.
3. A compound according to claim 2 wherein A is CH; L is S; M is N; and n is 0, or wherein A is CH; L is N; M is 0; and n is 0.
4. A compound according to claim 1 wherein A is CH or N; B is OCH3 ; one of L and M is N and the other is S or O; X is 2-, 3- or 4-pyridinyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 3- or 4-pyridazinyl or 2-1,3,5-triazinyl, any one of which is optionally substituted with halo, C1-4 alkyl, halo(C1-4)alkyl, C1-4 alkoxy, or halo(C1-4)alkoxy; and n is 0 or 1.
5. A compound according to claim 4 wherein A is CH; L is S; M is N; and n is 0, or wherein A is CH; L is N; M is 0; and n is 0.
6. A compound according to claim 1 wherein A is CH or N; B is OCH3 ; one of L and M is N and the other is S or 0; X is C3-6 cycloalkyl optionally substituted with C1-6 alkyl, halo(C1-4)alkyl, C3-6 cycloalkyl(C1-4)alkyl, C2-6 alkenyl or halo(C2-6)alkenyl; and n is 0 or 1.
7. A compound according to claim 6 wherein A is CH; L is S; M is N; and n is 0, or wherein A is CH; L is N; M is 0; and n is 0.
8. A fungicidal composition comprising a fungicidally effective amount of a compound according to claim 1 and a fungicidally acceptable carrier or diluent therefor.
9. A method of combating fungi which comprises applying to plants, to the seeds of plants or to the locus of the plants or seeds, a compound according to claim 1.
10. A insecticidal composition comprising an insecticidally or acaricidally effective amount of a compound according claim 1 and an insecticidally or acaricidally acceptable carrier or diluent therefor.
11. A method of combating insect or acarine pests which comprises applying to the locus of the pest, an insecticidally or acaricidally effective amount of a compound according to claim 1.
US08/144,179 1992-11-04 1993-10-27 Oxa- and thiadiazole derivatives Expired - Lifetime US5438066A (en)

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GB939301249A GB9301249D0 (en) 1993-01-22 1993-01-22 Fungicides
GB939301207A GB9301207D0 (en) 1993-01-22 1993-01-22 Insecticides
GB9309964 1993-05-14
GB939309964A GB9309964D0 (en) 1993-05-14 1993-05-14 Fungicides
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US6031107A (en) * 1995-10-18 2000-02-29 Bayer Aktiengesellschaft Fluoromethoxyacrylic acid derivatives and their use as pest control agents
US6096769A (en) * 1998-04-20 2000-08-01 American Cyanamid Company Fungicidal co-formulation
WO2000044222A2 (en) * 1999-01-29 2000-08-03 Laboratorio De Investigaciones Y Diagnosticos Agropecuarios, S.A. De C.V. Biological control of soil-borne fungal pathogens
US6423352B2 (en) * 1998-01-23 2002-07-23 Inulex Ltd. Alkaline preparations of Inula for the control of fungal diseases in plants
WO2004041798A1 (en) * 2002-11-08 2004-05-21 Sumitomo Chemical Company, Limited 1,2,4-thiadiazole compounds and use thereof
WO2004052280A2 (en) * 2002-12-10 2004-06-24 Imclone Systems Incorporated Anti-angiogenic compounds and their use in cancer treatment
US20040198633A1 (en) * 2001-05-23 2004-10-07 Roumen Antonov Identifying parasitic fungi of the organism, and treatment thereof
US20050181947A1 (en) * 2002-05-29 2005-08-18 Basf Agro Bv., Amhem (Nl)-Wadenswil-Branch Fungicidal seed treatment agent for oilseed rape
US20070232693A1 (en) * 2006-03-28 2007-10-04 Novus International, Inc. Compositions for treating infestation of plants by phytopathogenic microorganisms
US20090074887A1 (en) * 1993-04-28 2009-03-19 Bayer Cropscience Ag Fungicidal active compound combinations
US20110098177A1 (en) * 2006-03-28 2011-04-28 Novus International Inc. Methods and compositions of plant micronutrients
CZ303505B6 (en) * 2011-04-11 2012-10-24 Zentiva, K. S Process for preparing 2-ethoxy-1-((2?-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylates through their conversion to azilsartan

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US20090074887A1 (en) * 1993-04-28 2009-03-19 Bayer Cropscience Ag Fungicidal active compound combinations
US6337401B1 (en) * 1995-10-18 2002-01-08 Bayer Aktiengesellschaft Fluoromethoxyacrylic acid derivatives and their use as pest control agents
US6031107A (en) * 1995-10-18 2000-02-29 Bayer Aktiengesellschaft Fluoromethoxyacrylic acid derivatives and their use as pest control agents
US6423352B2 (en) * 1998-01-23 2002-07-23 Inulex Ltd. Alkaline preparations of Inula for the control of fungal diseases in plants
US6096769A (en) * 1998-04-20 2000-08-01 American Cyanamid Company Fungicidal co-formulation
WO2000044222A2 (en) * 1999-01-29 2000-08-03 Laboratorio De Investigaciones Y Diagnosticos Agropecuarios, S.A. De C.V. Biological control of soil-borne fungal pathogens
WO2000044222A3 (en) * 1999-01-29 2000-12-07 Invest Y Diagnosticos Agropecu Biological control of soil-borne fungal pathogens
US20040198633A1 (en) * 2001-05-23 2004-10-07 Roumen Antonov Identifying parasitic fungi of the organism, and treatment thereof
US20050181947A1 (en) * 2002-05-29 2005-08-18 Basf Agro Bv., Amhem (Nl)-Wadenswil-Branch Fungicidal seed treatment agent for oilseed rape
WO2004041798A1 (en) * 2002-11-08 2004-05-21 Sumitomo Chemical Company, Limited 1,2,4-thiadiazole compounds and use thereof
US7361675B2 (en) 2002-11-08 2008-04-22 Sumitomo Chemical Company Limited 1,2,4-thiadiazole compounds and use thereof
US20060167266A1 (en) * 2002-11-08 2006-07-27 Hideki Ihara 1,2,4- thiadiazole compounds and use thereof
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WO2004052280A3 (en) * 2002-12-10 2004-08-12 Imclone Systems Inc Anti-angiogenic compounds and their use in cancer treatment
WO2004052280A2 (en) * 2002-12-10 2004-06-24 Imclone Systems Incorporated Anti-angiogenic compounds and their use in cancer treatment
US20070232693A1 (en) * 2006-03-28 2007-10-04 Novus International, Inc. Compositions for treating infestation of plants by phytopathogenic microorganisms
US20110098177A1 (en) * 2006-03-28 2011-04-28 Novus International Inc. Methods and compositions of plant micronutrients
CZ303505B6 (en) * 2011-04-11 2012-10-24 Zentiva, K. S Process for preparing 2-ethoxy-1-((2?-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylates through their conversion to azilsartan

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